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414 values
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36
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873
rxn_insight_reaction
large_stringlengths
19
1.07k
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14
3.37k
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1
581
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1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
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346 values
rxn_insight_tag
large_stringlengths
64
64
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64
64
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large_stringlengths
5
288
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large_stringlengths
24
2.64k
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float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
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float64
-230
30.1k
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large_stringclasses
3 values
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float64
0
4k
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large_stringclasses
4 values
procedure_details
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1
23.6k
reference
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96 values
doi
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19 values
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large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-31c4a896e83a45cebbddcb3318f26ca3
CCOC(=O)Cn1ccc(=O)cc1.NN>>NNC(=O)Cn1ccc(=O)cc1
C(C)OC(CN1C=CC(C=C1)=O)=O.O.NN>>O=C1C=CN(C=C1)CC(=O)NN
CCO[C:3](=[O:4])[CH2:5][n:6]1[cH:7][cH:8][c:9](=[O:10])[cH:11][cH:12]1.[NH2:1][NH2:2]>>[NH2:1][NH:2][C:3](=[O:4])[CH2:5][n:6]1[cH:7][cH:8][c:9](=[O:10])[cH:11][cH:12]1
CCOC(=O)Cn1ccc(=O)cc1.NN
NNC(=O)Cn1ccc(=O)cc1
null
null
C(C)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
O=c1cc[nH]cc1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7;a:4].[N;D1;H2:5]-[NH2;D1;+0:6]>>[#7;a:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:6]-[N;D1;H2:5]
98
[{"value": 98.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (4-oxo-4H-pyridin-1-yl)-acetic acid ethyl ester (Bambury, Ronald E.; Edwards, Michael Louis; Miller, Laird Foulis. 4-Oxo-1-pyridinylpeniclliin and -cephalosporin derivatives. Ger. Offen. (1975)) in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 72 h. The mixture wa...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
c1ccncc1
HO-
C(C)O
null
null
CCOC(=O)Cn1ccc(=O)cc1.NN>C(C)O>NNC(=O)Cn1ccc(=O)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-609e140f7df14979a2f7e483e38df976
Cc1ncn(-c2ccc(Br)cc2C#N)c1C[N+](C)(C)C.NNC(=O)Cn1ccc(=O)cc1>>CC(C)OC(C)C.CO
BrC1=CC(=C(C=C1)N1C=NC(=C1C[N+](C)(C)C)C)C#N.[I-].O=C1C=CN(C=C1)CC(=O)NN>>CO.C(C)(C)OC(C)C
C[N+](C[c:3]1n(-c2ccc(Br)cc2C#N)cn[c:2]1[CH3:1])([CH3:6])[CH3:7].NN[C:8](Cn1cc[c:5](=[O:4])cc1)=[O:9]>>[CH3:1][CH:2]([CH3:3])[O:4][CH:5]([CH3:6])[CH3:7].[CH3:8][OH:9]
Cc1ncn(-c2ccc(Br)cc2C#N)c1C[N+](C)(C)C.NNC(=O)Cn1ccc(=O)cc1
CC(C)OC(C)C.CO
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
5f0b96cddc733e76e41f5cbe2934f2b24f6ef872ca06299474a8de03841efc70
67d3fc410ee0472bd8349ad7cd324cf228a4809901339c7d9fd10e6877802389
null
Br-c1:c:c:c(-n2:c:n:[c;H0;D3;+0:1](-[C;D1;H3:2]):[c;H0;D3;+0:3]:2-C-[N+](-C)(-[CH3;D1;+0:4])-[CH3;D1;+0:5]):c(-C#N):c:1.N-N-[C;H0;D3;+0:6](=[O;H0;D1;+0:7])-C-n1:c:c:[c;H0;D3;+0:8](=[O;H0;D1;+0:9]):c:c:1>>[C;D1;H3:2]-[CH;D3;+0:1](-[CH3;D1;+0:3])-[O;H0;D2;+0:9]-[CH;D3;+0:8](-[CH3;D1;+0:4])-[CH3;D1;+0:5].[CH3;D1;+0:6]-[OH...
33
[{"value": 33.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 84d, [3-(4-bromo-2-cyano-phenyl)-5-methyl-3H-imidazol-4-ylmethyl]-trimethyl-ammonium; iodide (example 84c) was reacted with (4-oxo-4H-pyridin-1-yl)-acetic acid hydrazide. After evaporation of the solvent the residue was concentrated and chromatographed (SiO2, dichloromethane:methanol=100:0 to 9...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Aromatic halide.Nitrile
Ether.Methanol
c1c[nH]cn1.c1ccccc1.c1ccncc1
null
null
HBr
null
null
null
Cc1ncn(-c2ccc(Br)cc2C#N)c1C[N+](C)(C)C.NNC(=O)Cn1ccc(=O)cc1>>CC(C)OC(C)C.CO
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5d37ce23a0404f77a3e8c04498ec18a9
CCOC(=O)CN(C)C=O.NN>>CN(C=O)CC(=O)NN
C(C)OC(CN(C)C=O)=O.O.NN>>N(N)C(=O)CN(C=O)C
CCO[C:6]([CH2:5][N:2]([CH3:1])[CH:3]=[O:4])=[O:7].[NH2:8][NH2:9]>>[CH3:1][N:2]([CH:3]=[O:4])[CH2:5][C:6](=[O:7])[NH:8][NH2:9]
CCOC(=O)CN(C)C=O.NN
CN(C=O)CC(=O)NN
null
null
C(C)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
null
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6].[N;D1;H2:7]-[NH2;D1;+0:8]>>[N;D1;H2:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6]
84
[{"value": 84.0, "product": "N(N)C(=O)CN(C=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (formyl-methyl-amino)-acetic acid ethyl ester (Hay, Michael P.; Wilson, William R.; Denny, William A. Tetrahedron (2000), 56(4), 645-657) in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 96 h. The mixture was concentrated and chromatographed (SiO2, dichloromethane...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
null
HO-
C(C)O
null
null
CCOC(=O)CN(C)C=O.NN>C(C)O>CN(C=O)CC(=O)NN
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8e6263eeedfa48e0bf3a0ae5bdc1fadb
CCOC(=O)Cn1c(C)cc(C)cc1=O.NN>>Cc1cc(C)n(CC(=O)NN)c(=O)c1
C(C)OC(CN1C(C=C(C=C1C)C)=O)=O.O.NN>>CC1=CC(N(C(=C1)C)CC(=O)NN)=O
CCO[C:8]([CH2:7][n:6]1[c:4]([CH3:5])[cH:3][c:2]([CH3:1])[cH:14][c:12]1=[O:13])=[O:9].[NH2:10][NH2:11]>>[CH3:1][c:2]1[cH:3][c:4]([CH3:5])[n:6]([CH2:7][C:8](=[O:9])[NH:10][NH2:11])[c:12](=[O:13])[cH:14]1
CCOC(=O)Cn1c(C)cc(C)cc1=O.NN
Cc1cc(C)n(CC(=O)NN)c(=O)c1
null
null
C(C)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
O=c1cccc[nH]1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7;a:4].[N;D1;H2:5]-[NH2;D1;+0:6]>>[#7;a:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:6]-[N;D1;H2:5]
null
[]
null
null
null
null
As described for example 112a, (4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester (Shusherina, N. P.; Slavyanova, O. V.; Petrova, L. K.; Levina, R. Ya. Zhurnal Organicheskoi Khimii (1972), 8(2), 387-9) in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 120 h. The mixture was concentrate...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
c1ccncc1
HO-
C(C)O
null
null
CCOC(=O)Cn1c(C)cc(C)cc1=O.NN>C(C)O>Cc1cc(C)n(CC(=O)NN)c(=O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3ed0c45c9a6c4e9cb8a5baa9d1aa71a3
COC(=O)C(O)C(F)(F)F.NN>>NNC(=O)C(O)C(F)(F)F
COC(C(O)C(F)(F)F)=O.O.NN>>FC(C(C(=O)NN)O)(F)F
CO[C:3](=[O:4])[CH:5]([OH:6])[C:7]([F:8])([F:9])[F:10].[NH2:1][NH2:2]>>[NH2:1][NH:2][C:3](=[O:4])[CH:5]([OH:6])[C:7]([F:8])([F:9])[F:10]
COC(=O)C(O)C(F)(F)F.NN
NNC(=O)C(O)C(F)(F)F
null
null
C(CCC)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
null
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[O;D1;H1:4])-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[N;D1;H2:9]-[NH2;D1;+0:10]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[C:3](-[O;D1;H1:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[N;D1;H2:9]
81
[{"value": 81.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, methyl-3,3,3-trifluoro-DL-lactate in butanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 16 h. The mixture was concentrated and the title compound was obtained as a light yellow oil (yield: 81%). MS: m/e=158.0 [M]+. Conditions: See reaction.notes.procedure_details. Work...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
null
HO-
C(CCC)O
null
null
COC(=O)C(O)C(F)(F)F.NN>C(CCC)O>NNC(=O)C(O)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-46c3720c154f4449815957fe8e3872cb
COC(=O)C(C)n1cncn1.NN>>CC(C(=O)NN)n1cncn1
COC(C(C)N1N=CN=C1)=O.O.NN>>N1(N=CN=C1)C(C(=O)NN)C
CO[C:3]([CH:2]([CH3:1])[n:7]1[cH:8][n:9][cH:10][n:11]1)=[O:4].[NH2:5][NH2:6]>>[CH3:1][CH:2]([C:3](=[O:4])[NH:5][NH2:6])[n:7]1[cH:8][n:9][cH:10][n:11]1
COC(=O)C(C)n1cncn1.NN
CC(C(=O)NN)n1cncn1
null
null
C(CCC)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
c1nc[nH]n1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[#7;a:4])-[C;D1;H3:5].[N;D1;H2:6]-[NH2;D1;+0:7]>>[#7;a:4]-[C:3](-[C;D1;H3:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[N;D1;H2:6]
91
[{"value": 91.0, "product": "N1(N=CN=C1)C(C(=O)NN)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (rac.)-2-[1,2,4]triazol-1-yl-propionic acid methyl ester in butanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 16 h. The mixture was concentrated and triturated with toluene to afford the title compound as a white solid (yield: 91%). MS: m/e=155.0 [M]+. Conditions: See...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
c1nc[nH]n1
HO-
C(CCC)O
null
null
COC(=O)C(C)n1cncn1.NN>C(CCC)O>CC(C(=O)NN)n1cncn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6db2cce419324c5cb504e5393ad45e68
CCOC(=O)CBr.Oc1ncccc1Br>>CCOC(=O)Cn1cccc(Br)c1=O
CCCCCCC.BrC=1C(=NC=CC1)O.BrCC(=O)OCC.C([O-])([O-])=O.[K+].[K+]>>C(C)OC(CN1C(C(=CC=C1)Br)=O)=O
Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].[n:7]1[cH:8][cH:9][cH:10][c:11]([Br:12])[c:13]1[OH:14]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][n:7]1[cH:8][cH:9][cH:10][c:11]([Br:12])[c:13]1=[O:14]
CCOC(=O)CBr.Oc1ncccc1Br
CCOC(=O)Cn1cccc(Br)c1=O
null
null
C(C)(=O)OCC
Acylation
OtherReaction
6dfdbac002000b49828e22c4b69d4571a0c0c3202697b85b5a08225e6955028a
5e9e0b01f8c9a1c10ac2bdfadca2d4bb3d9d0593654f2be0a33adb4d01012cf3
O=c1cccc[nH]1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].[Br;D1;H0:6]-[c:7]1:[c:8]:[c:9]:[c:10]:[n;H0;D2;+0:11]:[c;H0;D3;+0:12]:1-[OH;D1;+0:13]>>[Br;D1;H0:6]-[c:7]1:[c:8]:[c:9]:[c:10]:[n;H0;D3;+0:11](-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5]):[c;H0;D3;+0:12]:1=[O;H0;D1;+0:13]
55
[{"value": 55.0, "product": "C(C)OC(CN1C(C(=CC=C1)Br)=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 320a, 3-bromo-2-hydroxy-pyridine was reacted with ethyl bromoacetate and potassium carbonate. Extractive workup followed by chromatography (SiO2, heptane:ethyl acetate=100:0 to 50:50) afforded the title compound as a light yellow oil (yield: 55%), which was directly used in the next step. Condi...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester
c1ccncc1
c1ccncc1
c1ccncc1
HBr
C(C)(=O)OCC
null
null
CCOC(=O)CBr.Oc1ncccc1Br>C(C)(=O)OCC>CCOC(=O)Cn1cccc(Br)c1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-85bae26dc8f64b46b36b6910f0c0b0d1
CCOC(=O)Cn1cccc(Br)c1=O.NN>>NNC(=O)Cn1cccc(Br)c1=O
C(C)OC(CN1C(C(=CC=C1)Br)=O)=O.O.NN>>BrC=1C(N(C=CC1)CC(=O)NN)=O
CCO[C:3](=[O:4])[CH2:5][n:6]1[cH:7][cH:8][cH:9][c:10]([Br:11])[c:12]1=[O:13].[NH2:1][NH2:2]>>[NH2:1][NH:2][C:3](=[O:4])[CH2:5][n:6]1[cH:7][cH:8][cH:9][c:10]([Br:11])[c:12]1=[O:13]
CCOC(=O)Cn1cccc(Br)c1=O.NN
NNC(=O)Cn1cccc(Br)c1=O
null
null
C(CCC)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
O=c1cccc[nH]1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7;a:4].[N;D1;H2:5]-[NH2;D1;+0:6]>>[#7;a:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:6]-[N;D1;H2:5]
62
[{"value": 62.0, "product": "BrC=1C(N(C=CC1)CC(=O)NN)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (3-bromo-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester in butanol was reacted with hydrazine hydrate (1.2 equivalents) at reflux for 16 h. The precipitate was filtered and triturated with hot methanol to afford the title compound as an off-white solid (yield: 62%). MS: m/e=244.2/246.2 [M...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
c1ccncc1
HO-
C(CCC)O
null
null
CCOC(=O)Cn1cccc(Br)c1=O.NN>C(CCC)O>NNC(=O)Cn1cccc(Br)c1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3aad6f459cfe4326ad8c19288ce80229
CC1C=NNC1=O.CCOC(=O)CBr>>CCOC(=O)Cn1cc(C)c(=O)[nH]1
CCCCCCC.CC1C=NNC1=O.BrCC(=O)OCC.C([O-])([O-])=O.[K+].[K+]>>C(C)OC(CN1NC(C(=C1)C)=O)=O
[N:7]1=[CH:8][CH:9]([CH3:10])[C:11](=[O:12])[NH:13]1.Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][n:7]1[cH:8][c:9]([CH3:10])[c:11](=[O:12])[nH:13]1
CC1C=NNC1=O.CCOC(=O)CBr
CCOC(=O)Cn1cc(C)c(=O)[nH]1
null
null
C(C)(=O)OCC
Aromatic Heterocycle Formation
OtherReaction
20c101320b8ac86519a3347e507965089cbf375b3d82b6c2e7839bdb6c5ac378
c7c13ec804ee909cea6287c19c05017bf2ccbeecbbfe7a5965d1d762a284c97f
O=c1cc[nH][nH]1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].[C;D1;H3:6]-[CH;D3;+0:7]1-[CH;D2;+0:8]=[N;H0;D2;+0:9]-[NH;D2;+0:10]-[C;H0;D3;+0:11]-1=[O;D1;H0:12]>>[C:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[n;H0;D3;+0:9]1:[cH;D2;+0:8]:[c;H0;D3;+0:7](-[C;D1;H3:6]):[c;H0;D3;+0:11](=[O;D1;H0:12]):[nH;D2;+0:10]:1
16
[{"value": 16.0, "product": "C(C)OC(CN1NC(C(=C1)C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 320a, 4-methyl-2-pyrazolin-5-one was reacted with ethyl bromoacetate and potassium carbonate. Extractive workup followed by chromatography (SiO2, heptane:ethyl acetate=100:0 to 50:50) afforded the title compound as a white solid (yield: 16%). MS: m/e=185.0 [M+H]+. Conditions: See reaction.notes...
10.6084/m9.figshare.5104873.v1
null
Hydrazone amide.Primary halide.Ester
Ester
C1=NNCC1
c1cn[nH]c1
c1cn[nH]c1
HBr
C(C)(=O)OCC
null
null
CC1C=NNC1=O.CCOC(=O)CBr>C(C)(=O)OCC>CCOC(=O)Cn1cc(C)c(=O)[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-108e5e87af074ab59bf196fe349f8eac
COC(=O)C(O)C1CC1.NN>>NNC(=O)C(O)C1CC1
COC(C(O)C1CC1)=O.O.NN>>C1(CC1)C(C(=O)NN)O
CO[C:3](=[O:4])[CH:5]([OH:6])[CH:7]1[CH2:8][CH2:9]1.[NH2:1][NH2:2]>>[NH2:1][NH:2][C:3](=[O:4])[CH:5]([OH:6])[CH:7]1[CH2:8][CH2:9]1
COC(=O)C(O)C1CC1.NN
NNC(=O)C(O)C1CC1
null
null
CO
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
C1CC1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[O;D1;H1:5].[N;D1;H2:6]-[NH2;D1;+0:7]>>[C:4]-[C:3](-[O;D1;H1:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[N;D1;H2:6]
69
[{"value": 69.0, "product": "C1(CC1)C(C(=O)NN)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (rac.)-2-cyclopropyl-2-hydroxy-acetic acid methyl ester (Newall, Christopher Earle; Foxton, Michael Walter; Hartley, Charles David; Looker, Brian Edgar. Cephalosporin antibiotics. Eur. Pat. Appl. (1985), 57 pp) in methanol was reacted with hydrazine hydrate (1.0 equivalent) at rt for 76 h...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
C1CC1
HO-
CO
null
null
COC(=O)C(O)C1CC1.NN>CO>NNC(=O)C(O)C1CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-18a74b86c985445bbe1810535f597593
CCOC(=O)CN1CCOC1=O.NN>>NNC(=O)CN1CCOC1=O
C(C)OC(CN1C(OCC1)=O)=O.O.NN>>O=C1OCCN1CC(=O)NN
CCO[C:3](=[O:4])[CH2:5][N:6]1[CH2:7][CH2:8][O:9][C:10]1=[O:11].[NH2:1][NH2:2]>>[NH2:1][NH:2][C:3](=[O:4])[CH2:5][N:6]1[CH2:7][CH2:8][O:9][C:10]1=[O:11]
CCOC(=O)CN1CCOC1=O.NN
NNC(=O)CN1CCOC1=O
null
null
C(C)O
Acylation
Aminolysis of esters
2e40a14c7d71c6b9001f460fbb953805c923b2db988c8c04f234b9bb5f04424f
3b636feb164ef0f3c8a4f1764f18a25b9eee32ed1463e3bb4b6f1becb871ca74
O=C1NCCO1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5](=[O;D1;H0:6])-[#8:7].[N;D1;H2:8]-[NH2;D1;+0:9]>>[#8:7]-[C:5](=[O;D1;H0:6])-[#7:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[N;D1;H2:8]
77
[{"value": 77.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
As described for example 112a, (2-oxo-oxazolidin-3-yl)-acetic acid ethyl ester (Potts, Kevin T.; Bhattacharjee, Debkumar; Kanemasa, Shuji. Journal of Organic Chemistry (1980), 45(24), 4985-8) in ethanol was reacted with hydrazine hydrate (1.0 equivalent) at rt for 72 h. All volatiles were evaporated, the residue was ch...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ester
Acylhydrazine
null
null
C1COC[NH]1
HO-
C(C)O
null
null
CCOC(=O)CN1CCOC1=O.NN>C(C)O>NNC(=O)CN1CCOC1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-520232ade3bd4eb4b79877e21eb1d435
O=C1CN2CCC1CC2>>C1CN2CCC1C1(CO1)C2
O.[I-].C[S+](=O)(C)C.[H-].[Na+].N12CC(C(CC1)CC2)=O>>O1C2(C1)CN1CCC2CC1
[CH2:1]1[CH2:2][N:3]2[CH2:4][CH2:5][CH:6]1[C:7](=[O:9])[CH2:10]2>>[CH2:1]1[CH2:2][N:3]2[CH2:4][CH2:5][CH:6]1[C:7]1([CH2:8][O:9]1)[CH2:10]2
O=C1CN2CCC1CC2
C1CN2CCC1C1(CO1)C2
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
1d2de7e8761d4ac43c89e1777f675ff6bbb77776d7762a997d103a4f39a2764f
65a8af0997ec9f56fa44fac9e6db8d8aeec07e535d6b4d216a6180693919dc05
C1CN2CCC1C1(CO1)C2
[O;H0;D1;+0:1]=[C;H0;D3;+0:2]1-[C:3]-[#7:4]2-[C:5]-[C:6]-[C:7]-1-[C:8]-[C:9]-2>>[C:3]1-[#7:4]2-[C:5]-[C:6]-[C:7](-[C:8]-[C:9]-2)-[C;H0;D4;+0:2]-12-[C:10]-[O;H0;D2;+0:1]-2
83.1
[{"value": 83.0, "product": "O1C2(C1)CN1CCC2CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.1, "product": "O1C2(C1)CN1CCC2CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
67.5
CELSIUS
1
HOUR
A mixture of trimethylsulfoxonium iodide (16.10 g, 73.2, mmol) and a dispersion of sodium hydride (60% in oil, 3.00 g, 75.0 mmol) in anhydrous dimethyl sulfoxide was stirred at room temperature under nitrogen for 30 minutes. Quinuclidin-3-one (7.05 g, 56.3 mmol) was then added as a solid portionwise, and the resulting ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Ether
C1CN2CCC1CC2
C1CN2CCC1C1(CO1)C2
C1CN2CCC1C1(CO1)C2
Other
CS(=O)C
67.5
1
O=C1CN2CCC1CC2>CS(=O)C>C1CN2CCC1C1(CO1)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0ad948d750664b37908a63ff8f7e4490
CC(=O)OC(C)(C)C.O=C1CN2CCC1CC2>>CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2
N12CC(C(CC1)CC2)=O.C(C)(=O)OC(C)(C)C.C(C)(C)NC(C)C.C(CCC)[Li]>>C(C)(C)(C)OC(CC1(CN2CCC1CC2)O)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[CH3:8].[C:9]1(=[O:10])[CH2:11][N:12]2[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]2>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[CH2:8][C:9]1([OH:10])[CH2:11][N:12]2[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]2
CC(=O)OC(C)(C)C.O=C1CN2CCC1CC2
CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2
null
null
O1CCCC1.O
C-C Coupling
OtherReaction
94d6803c7d74b3309832e8415c4e91ad841bbe8c96cf64395c33ff657c37d792
044a18e4d3accc9215121cf8386364d4c22240176cddbc024e8f77ed5574d3a0
C1CN2CCC1CC2
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](-[CH3;D1;+0:7])=[O;D1;H0:8].[O;H0;D1;+0:9]=[C;H0;D3;+0:10]1-[C:11]-[#7:12]2-[C:13]-[C:14]-[C:15]-1-[C:16]-[C:17]-2>>[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](=[O;D1;H0:8])-[CH2;D2;+0:7]-[C;H0;D4;+0:10]1(-[OH;D1;+0:9])-[C:11]-[#7:12]2-[C:13]-[C:...
null
[]
-78
CELSIUS
40
MINUTE
To a solution of diisopropylamine (6.7 mL) in tetrahydrofuran (THF) (20 mL) at 0° C. was added n-butyllithium (2.3M in hexanes; 20 mL). The reaction mixture was stirred for 40 minutes and then cooled to −78° C. To this mixture a solution of t-butyl acetate (6.4 mL) in THF (10 mL) was added dropwise and stirring was con...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester
Ester.Tertiary alcohol
C1CN2CCC1CC2
C1CN2CCC1CC2
C1CN2CCC1CC2
null
O1CCCC1.O
-78
0.666667
CC(=O)OC(C)(C)C.O=C1CN2CCC1CC2>O1CCCC1.O>CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-580edcc21b3943089555aff97a359acc
CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2>>COC(=O)CC1(O)CN2CCC1CC2
FC(C(=O)O)(F)F.C(C)(C)(C)OC(CC1(CN2CCC1CC2)O)=O>>COC(CC1(CN2CCC1CC2)O)=O
C[C:1](C)(C)[O:2][C:3](=[O:4])[CH2:5][C:6]1([OH:7])[CH2:8][N:9]2[CH2:10][CH2:11][CH:12]1[CH2:13][CH2:14]2>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][C:6]1([OH:7])[CH2:8][N:9]2[CH2:10][CH2:11][CH:12]1[CH2:13][CH2:14]2
CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2
COC(=O)CC1(O)CN2CCC1CC2
null
null
ClCCl
Miscellaneous
OtherReaction
65c8f61c086a235ce6692c51186a0187b2fa4d47add33293a3d7824255d1a4bf
019584698d6f4e780dc33c58bbe427f505956c44d516240fec11049769c33a01
C1CN2CCC1CC2
C-[C;H0;D4;+0:1](-C)(-C)-[#8:2]-[C:3](-[C:4])=[O;D1;H0:5]>>[C:4]-[C:3](=[O;D1;H0:5])-[#8:2]-[CH3;D1;+0:1]
48.6
[{"value": 48.6, "product": "COC(CC1(CN2CCC1CC2)O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
Trifluoroacetic acid (40 mL) was added dropwise over 15 minutes to a solution of 2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetic acid t-butyl ester (15.7 g) in anhydrous dichloromethane (40 mL) at 0° C. The mixture was stirred for 24 hours at room temperature, then the solvent was evaporated under reduced pressure. The...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Ester
null
null
C1CN2CCC1CC2
Other
ClCCl
null
24
CC(C)(C)OC(=O)CC1(O)CN2CCC1CC2>ClCCl>COC(=O)CC1(O)CN2CCC1CC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a4aa0c519b2443368aaf9af2257110b9
O=C1CN2CCC1CC2>>C=CC1(O)CN2CCC1CC2
Cl.N12CC(C(CC1)CC2)=O.C(=C)[Mg]Br.[OH-].[Na+]>>C(=C)C1(CN2CCC1CC2)O
[C:3]1(=[O:4])[CH2:5][N:6]2[CH2:7][CH2:8][CH:9]1[CH2:10][CH2:11]2>>[CH2:1]=[CH:2][C:3]1([OH:4])[CH2:5][N:6]2[CH2:7][CH2:8][CH:9]1[CH2:10][CH2:11]2
O=C1CN2CCC1CC2
C=CC1(O)CN2CCC1CC2
null
null
O1CCCC1
Miscellaneous
OtherReaction
f21ddbb27da853085157398477990264463ccc31727c7da86599b64d000ecee1
2ce956c609b76ee2dc626ad09e785d954b7df9a7379fec6f4a0d038e8e2d1b2b
C1CN2CCC1CC2
[O;H0;D1;+0:1]=[C;H0;D3;+0:2]1-[C:3]-[#7:4]2-[C:5]-[C:6]-[C:7]-1-[C:8]-[C:9]-2>>[C;D1;H2:10]=[C:11]-[C;H0;D4;+0:2]1(-[OH;D1;+0:1])-[C:3]-[#7:4]2-[C:5]-[C:6]-[C:7]-1-[C:8]-[C:9]-2
54
[{"value": 54.0, "product": "C(=C)C1(CN2CCC1CC2)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
Under an argon atmosphere, a solution of 3-quinuclidinone (1.25 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) was added over 15 minutes to a 1 M solution of vinylmagnesium bromide in tetrahydrofuran (20 mL, 20 mmol) at 0° C. to 5° C., stirred at room temperature for 24 hours, cooled to 0° C., and acidified to pH 1 w...
10.6084/m9.figshare.5104873.v1
null
Ketone
Tertiary alcohol.Vinyl
C1CN2CCC1CC2
C1CN2CCC1CC2
C1CN2CCC1CC2
Other
O1CCCC1
null
24
O=C1CN2CCC1CC2>O1CCCC1>C=CC1(O)CN2CCC1CC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ad0a923fc5134e3ead3d7adfab6b63fc
CI.Oc1ncccc1Br>>COc1ncccc1Br
BrC=1C(=NC=CC1)O.IC>>BrC=1C(=NC=CC1)OC
I[CH3:1].[OH:2][c:3]1[n:4][cH:5][cH:6][cH:7][c:8]1[Br:9]>>[CH3:1][O:2][c:3]1[n:4][cH:5][cH:6][cH:7][c:8]1[Br:9]
CI.Oc1ncccc1Br
COc1ncccc1Br
null
C([O-])([O-])=O.[Ag+2]
C1=CC=CC=C1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
b8b041187bac58376aae824630608e7deb49a01db3d652291f8b379c10d4e434
0f0966e3597a58033417ecee71659f4d0c082f95d46b1e52c95541e6e4a59086
c1ccncc1
I-[CH3;D1;+0:1].[OH;D1;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]>>[CH3;D1;+0:1]-[O;H0;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]
62.5
[{"value": 62.0, "product": "BrC=1C(=NC=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.5, "product": "BrC=1C(=NC=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
Under an argon atmosphere, a mixture of 3-bromo-2-hydroxypyridine (3.49 g, 20 mmol), silver carbonate (3.67 g, 13.31 mmol), and iodomethane (1.5 mL, 24.1 mmol) in benzene (30 mL) was stirred in the dark at 40° C. to 50° C. for 24 hours, cooled in an ice bath, and filtered. The filtrate was washed once with 2% aqueous s...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Ether
null
null
c1ccncc1
HI
C([O-])([O-])=O.[Ag+2].C1=CC=CC=C1
null
24
CI.Oc1ncccc1Br>C([O-])([O-])=O.[Ag+2].C1=CC=CC=C1>COc1ncccc1Br
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eacd2701b2e144d580e592027d361c05
BrBr.c1cnc2c(c1)CC1(CN3CCC1CC3)O2>>Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2
C([O-])([O-])=O.[Na+].[Na+].O1C2(CC=3C1=NC=CC3)CN3CCC2CC3.C(C)(=O)[O-].[Na+].BrBr>>BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[Br:1].[cH:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2>>[Br:1][c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2
BrBr.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
C(C)(=O)O
Functional Group Interconversion
Bromination
52873c08474b84aeaea35f3c651ab8ce4e7921a0270815f2005959aaaae0cacf
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Br-[Br;H0;D1;+0:1].[#8:2]-[c:3]1:[#7;a:4]:[c:5]:[cH;D2;+0:6]:[c:7]:[c:8]:1>>[#8:2]-[c:3]1:[#7;a:4]:[c:5]:[c;H0;D3;+0:6](-[Br;H0;D1;+0:1]):[c:7]:[c:8]:1
81
[{"value": 81.0, "product": "BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.1, "product": "BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (100 mg, 0.462 mmol) and sodium acetate (410 mg, 5 mmol) in 50% aqueous acetic acid (4 mL) was heated to 60° C. Bromine (0.100 mL, 1.94 mmol) was added via a syringe over 10 minutes, and the solution was then heated under reflux for 1 hour. Th...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr
C(C)(=O)O
null
null
BrBr.c1cnc2c(c1)CC1(CN3CCC1CC3)O2>C(C)(=O)O>Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d25f2503cfbe47ee97e0b4ecb90838d9
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.OB(O)c1ccccc1>>c1ccc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)cc1
C([O-])([O-])=O.[Na+].[Na+].BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C1(=CC=CC=C1)B(O)O.COCCOC>>C1(=CC=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[c:5]1[cH:6][n:7][c:8]2[c:9]([cH:10]1)[CH2:11][C:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2.OB(O)[c:4]1[cH:3][cH:2][cH:1][cH:22][cH:21]1>>[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[cH:6][n:7][c:8]3[c:9]([cH:10]2)[CH2:11][C:12]2([CH2:13][N:14]4[CH2:15][CH2:16][CH:17]2[CH2:18][CH2:19]4)[O:20]3)[cH:21][...
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.OB(O)c1ccccc1
c1ccc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)cc1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
C(C)O
C-C Coupling
Suzuki coupling with boronic acids
5532cdf25c636ff194e1c9e6a6006682a2770fdb59d30b0bcbc1b23d8404c91e
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)cc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4](:[#7;a:5]:[c:6]:1)-[#8:7].O-B(-O)-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]>>[#8:7]-[c:4]1:[#7;a:5]:[c:6]:[c;H0;D3;+0:1](-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]):[c:2]:[c:3]:1
68.5
[{"value": 68.0, "product": "C1(=CC=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.5, "product": "C1(=CC=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Under a nitrogen atmosphere, 5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (118 mg, 0.4 mmol), phenylboronic acid (54 mg, 0.443 mmol), and tetrakis(triphenylphosphine)palladium(0) (11 mg, 2.3 mol %) were stirred in a solution of 1,2-dimethoxyethane (3 mL) and ethanol (0.75 mL) containing 2M aqu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C(C)O
null
null
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.OB(O)c1ccccc1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C(C)O>c1ccc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e2bcaeee572442e29ef44100865b22cc
O=[N+]([O-])O.c1cnc2c(c1)CC1(CN3CCC1CC3)O2>>O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2
O1C2(CC=3C1=NC=CC3)CN3CCC2CC3.[N+](=O)(O)[O-].C([O-])([O-])=O.[Na+].[Na+]>>[N+](=O)([O-])C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
O[N+:2](=[O:1])[O-:3].[cH:4]1[cH:5][n:6][c:7]2[c:8]([cH:9]1)[CH2:10][C:11]1([CH2:12][N:13]3[CH2:14][CH2:15][CH:16]1[CH2:17][CH2:18]3)[O:19]2>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][n:6][c:7]2[c:8]([cH:9]1)[CH2:10][C:11]1([CH2:12][N:13]3[CH2:14][CH2:15][CH:16]1[CH2:17][CH2:18]3)[O:19]2
O=[N+]([O-])O.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
S(O)(O)(=O)=O
Functional Group Addition
Aromatic nitration with HNO3
dadd112342dc5b925b662cd59df7d6fbcfbe4ee80f945deaec3673160c268cd2
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[#8:4]-[c:5]1:[#7;a:6]:[c:7]:[cH;D2;+0:8]:[c:9]:[c:10]:1>>[#8:4]-[c:5]1:[#7;a:6]:[c:7]:[c;H0;D3;+0:8](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:9]:[c:10]:1
51
[{"value": 51.0, "product": "[N+](=O)([O-])C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.0, "product": "[N+](=O)([O-])C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (325 mg, 1.5 mmol) and fuming nitric acid (0.27 mL, 5.74 mmol) in sulfuric acid (0.75 mL) was heated at 70° C. to 80° C. for 24 hours. The resulting viscous solution was poured onto 15 g of ice and basified to pH>10 with solid sodium carbonate....
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HO-
S(O)(O)(=O)=O
null
null
O=[N+]([O-])O.c1cnc2c(c1)CC1(CN3CCC1CC3)O2>S(O)(O)(=O)=O>O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-400e8640d6b147e2a244d50dc9215ce0
O=[N+]([O-])O.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2>>O=[N+]([O-])c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
C([O-])([O-])=O.[K+].[K+].[N+](=O)(O)[O-].O1[C@@]2(CC=3C1=NC=CC3)CN3CCC2CC3.O>>[N+](=O)([O-])C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2
O[N+:2](=[O:1])[O-:3].[cH:4]1[cH:5][n:6][c:7]2[c:8]([cH:9]1)[CH2:10][C@@:11]1([CH2:12][N:13]3[CH2:14][CH2:15][CH:16]1[CH2:17][CH2:18]3)[O:19]2>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][n:6][c:7]2[c:8]([cH:9]1)[CH2:10][C@@:11]1([CH2:12][N:13]3[CH2:14][CH2:15][CH:16]1[CH2:17][CH2:18]3)[O:19]2
O=[N+]([O-])O.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
O=[N+]([O-])c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
null
null
S(O)(O)(=O)=O
Functional Group Addition
Aromatic nitration with HNO3
ca6cf43857203756cf55b7572ca5ed70b01ca7c9564230f2a416edb151d1eb5a
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[#8:4]-[c:5]1:[#7;a:6]:[c:7]:[cH;D2;+0:8]:[c:9]:[c:10]:1>>[#8:4]-[c:5]1:[#7;a:6]:[c:7]:[c;H0;D3;+0:8](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:9]:[c:10]:1
98.6
[{"value": 98.0, "product": "[N+](=O)([O-])C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.6, "product": "[N+](=O)([O-])C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
67.5
CELSIUS
1
HOUR
(R)-(−)-Spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (3.03 g, 14 mmol) was dissolved in concentrated sulfuric acid (7 mL) at 0-5 ° C., fuming nitric acid (3.3 mL, 70.2 mmol) was added over 10 minutes, the mixture was stirred for 1 hour, and heated at 65-70° C. for 24 hours. Cooled, poured onto ice (20...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
HO-
S(O)(O)(=O)=O
67.5
1
O=[N+]([O-])O.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2>S(O)(O)(=O)=O>O=[N+]([O-])c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f99a1b3a022b433494a5dafe732c7480
O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2>>Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
[N+](=O)([O-])C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.[H][H]>>NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
O=[N+:1]([O-])[c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2>>[NH2:1][c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2
O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
[Pd]
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]-[#8:7]>>[#8:7]-[c:6]:[#7;a:5]:[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
98
[{"value": 98.0, "product": "NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.9, "product": "NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 5′-nitrospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (1.4 g, 5.36 mmol), and 10% palladium on carbon (48% water wet, 270 mg) in methanol (90 mL) was hydrogenated for 1 hour at 50 psi of hydrogen. The catalyst was filtered off through a pad of celite and the solvent was evaporated under re...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Other
[Pd].CO
null
null
O=[N+]([O-])c1cnc2c(c1)CC1(CN3CCC1CC3)O2>[Pd].CO>Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2c93104eb5f94015a581ed27c197d6b4
O=[N+]([O-])c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2>>Nc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
[N+](=O)([O-])C=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2>>NC=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2
O=[N+:1]([O-])[c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C@:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2>>[NH2:1][c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C@:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2
O=[N+]([O-])c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
Nc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
null
null
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]-[#8:7]>>[#8:7]-[c:6]:[#7;a:5]:[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
92
[{"value": 92.0, "product": "NC=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.6, "product": "NC=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
The enantiomer (S)-(+)-5′nitrospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (6.85 g, 26.2 mmol) treated in the same way as described in example 8A in ammoniated methanol provided the title compound (5.55 g, 24 mmol, 92%): electrospray MS (m/z, relative intensity) 232 ([MH]+, 100). Conditions: See react...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
Other
CO
null
null
O=[N+]([O-])c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2>CO>Nc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4c4e218f34534cd1833e59d19281cd2d
Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2.O=C=Nc1ccccc1>>O=C(Nc1ccccc1)Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
C1(=CC=CC=C1)N=C=O.NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2>>C1(=CC=CC=C1)NC(=O)NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
[NH2:10][c:11]1[cH:12][n:13][c:14]2[c:15]([cH:16]1)[CH2:17][C:18]1([CH2:19][N:20]3[CH2:21][CH2:22][CH:23]1[CH2:24][CH2:25]3)[O:26]2.[O:1]=[C:2]=[N:3][c:4]1[cH:5][cH:6][cH:7][cH:8][cH:9]1>>[O:1]=[C:2]([NH:3][c:4]1[cH:5][cH:6][cH:7][cH:8][cH:9]1)[NH:10][c:11]1[cH:12][n:13][c:14]2[c:15]([cH:16]1)[CH2:17][C:18]1([CH2:19][N...
Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2.O=C=Nc1ccccc1
O=C(Nc1ccccc1)Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
O1CCCC1
Acylation
Urea synthesis via isocyanate and primary amine
d39cd7dc52a79bb265ff8ef61ef7bf9dc7f7b5fb0150fcb4881bdfb18ab9c380
a5dc801930c765d2a435a0a2973e50163c305ba8e7641d6adbcc1550b7b96de7
O=C(Nc1ccccc1)Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
[#8:1]-[c:2]:[#7;a:3]:[c:4]:[c:5](-[NH2;D1;+0:6]):[c:7].[O;D1;H0:8]=[C;H0;D2;+0:9]=[N;H0;D2;+0:10]-[c:11](:[c:12]):[c:13]>>[#8:1]-[c:2]:[#7;a:3]:[c:4]:[c:5](-[NH;D2;+0:6]-[C;H0;D3;+0:9](=[O;D1;H0:8])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:7]
86
[{"value": 86.0, "product": "C1(=CC=CC=C1)NC(=O)NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.0, "product": "C1(=CC=CC=C1)NC(=O)NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
Under a nitrogen atmosphere, phenyl isocyanate (0.056 mL, 0.515 mmol) was added to a suspension of 5′-aminospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (119 mg, 0.514 mmol) in anhydrous tetrahydrofuran (5 mL) and stirred for 12 hours. The solvent was evaporated under reduced pressure and the residue p...
10.6084/m9.figshare.5104873.v1
null
Isocyanate.Primary amine
Urea
null
null
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
O1CCCC1
null
12
Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2.O=C=Nc1ccccc1>O1CCCC1>O=C(Nc1ccccc1)Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-340e8386b3ab433387d1baaaf25bcefb
C=O.Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2>>CNc1cnc2c(c1)CC1(CN3CCC1CC3)O2
[BH4-].[Na+].NC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C=O.[Na].[OH-].[K+]>>CNC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
O=[CH2:1].[NH2:2][c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2>>[CH3:1][NH:2][c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2
C=O.Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2
CNc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
CO
Heteroatom Alkylation and Arylation
Reductive methylation of primary amine with formaldehyde
51d235def9103cd7a524cbedb590276839772d481304df37a121e64cb81721f4
cf32f1267c674fd84d46b8a676a46bd4e3a018dea282d34ea9ab93d79b66d0ee
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
O=[CH2;D1;+0:1].[#8:2]-[c:3]:[#7;a:4]:[c:5]:[c:6](-[NH2;D1;+0:7]):[c:8]>>[#8:2]-[c:3]:[#7;a:4]:[c:5]:[c:6](-[NH;D2;+0:7]-[CH3;D1;+0:1]):[c:8]
64
[{"value": 64.0, "product": "CNC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.0, "product": "CNC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
1
HOUR
Under a nitrogen atmosphere, sodium (50 mg, 2.17 mmol) was slowly added (exothermic) to methanol (1 mL) and stirred for 1 hour. 5′-Aminospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (115 mg, 0.5 mmol) and paraformaldehyde (35 mg, 1.17 mmol) were added and stirred for 16 hours. The reaction was heated a...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Primary amine
Secondary amine
null
null
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Other
CO
50
1
C=O.Nc1cnc2c(c1)CC1(CN3CCC1CC3)O2>CO>CNc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-37fc548b8c7243d2b119e04116c1608c
Brc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2.C=Cc1ccccc1>>C(=C/c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2)\c1ccccc1
BrC=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2.C=CC1=CC=CC=C1.C(C)N(CC)CC>>C1(=CC=CC=C1)/C=C/C=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2
Br[c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C@:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2.[CH:1](=[CH2:2])[c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1>>[CH:1](=[CH:2]/[c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C@:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2)\[c:19...
Brc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2.C=Cc1ccccc1
C(=C/c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2)\c1ccccc1
null
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C
C(C)#N
C-C Coupling
Heck terminal vinyl
e90651fdb05c01d851278e5ae382bcae6fa85b26ae953ac6a6c1431f21633399
4b186811a4930853b446d93d9faa39b267bddb9ce0b8021bda5c5a3b2bc69f0b
C(=C/c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2)\c1ccccc1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7].[CH2;D1;+0:8]=[C:9]-[c:10]>>[#8:7]-[c:4]1:[#7;a:3]:[c:2]:[c;H0;D3;+0:1](/[CH;D2;+0:8]=[C:9]/[c:10]):[c:6]:[c:5]:1
55
[{"value": 55.0, "product": "C1(=CC=CC=C1)/C=C/C=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.9, "product": "C1(=CC=CC=C1)/C=C/C=1C=C2C(=NC1)O[C@]1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A solution of (S)-(+)-5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (150 mg, 0.51 mmol), styrene (0.07 mL, 0.61 mmol), palladium(II)acetate (1.2 mg, 0.0053 mmol), tri-o-tolylphosphine (6.4 mg, 0.021 mmol), and triethylamine (0.5 mL, 3.6 mmol) in anhydrous acetonitrile (0.5 mL), in a heavy-walle...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Vinyl
null
c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
c1ccccc1.c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2
HBr
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.C(C)#N
100
null
Brc1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2.C=Cc1ccccc1>C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.C(C)#N>C(=C/c1cnc2c(c1)C[C@]1(CN3CCC1CC3)O2)\c1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-81734a9017f04404bb22a1ceee0a0fbd
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C1CNC1>>c1nc2c(cc1N1CCC1)C[C@@]1(CN3CCC1CC3)O2
BrC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2.N1CCC1.CC(C)([O-])C.[Na+].C1(=CC=CC=C1)P(C1=C(C2=CC=CC=C2C=C1)C1=C(C=CC2=CC=CC=C12)P(C1=CC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1>>N1(CCC1)C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2
Br[c:6]1[cH:1][n:2][c:3]2[c:4]([cH:5]1)[CH2:11][C@@:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2.[NH:7]1[CH2:8][CH2:9][CH2:10]1>>[cH:1]1[n:2][c:3]2[c:4]([cH:5][c:6]1[N:7]1[CH2:8][CH2:9][CH2:10]1)[CH2:11][C@@:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C1CNC1
c1nc2c(cc1N1CCC1)C[C@@]1(CN3CCC1CC3)O2
null
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd]
O1CCCC1
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
79956164f14638ce7279e5ff4e5a606cb458c293e21fea7c157a94bae280fe56
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1nc2c(cc1N1CCC1)C[C@@]1(CN3CCC1CC3)O2
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7].[C:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[#8:7]-[c:4]1:[#7;a:3]:[c:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:11]2-[C:8]-[C:9]-[C:10]-2):[c:6]:[c:5]:1
null
[]
75
CELSIUS
null
null
(R)-(−)-5′-Bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (295 mg, 1 mmol), azetidine (0.101 mL, 1.5 mmol), sodium tert-butoxide (135 mg, 1.4 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (62 mg, 0.1 mmol) and anhydrous tetrahydrofuran ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNC1.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
C1C[NH]C1.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
C1C[NH]C1.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
HBr
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].O1CCCC1
75
null
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C1CNC1>C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].O1CCCC1>c1nc2c(cc1N1CCC1)C[C@@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bd16bf666c344fe7a484df657614c6e0
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C=Cc1ccccn1>>C(=Cc1ccccn1)c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
BrC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2.C(=C)C1=NC=CC=C1>>N1=C(C=CC=C1)C=CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2
Br[c:9]1[cH:10][n:11][c:12]2[c:13]([cH:14]1)[CH2:15][C@@:16]1([CH2:17][N:18]3[CH2:19][CH2:20][CH:21]1[CH2:22][CH2:23]3)[O:24]2.[CH2:1]=[CH:2][c:3]1[cH:4][cH:5][cH:6][cH:7][n:8]1>>[CH:1](=[CH:2][c:3]1[cH:4][cH:5][cH:6][cH:7][n:8]1)[c:9]1[cH:10][n:11][c:12]2[c:13]([cH:14]1)[CH2:15][C@@:16]1([CH2:17][N:18]3[CH2:19][CH2:20...
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C=Cc1ccccn1
C(=Cc1ccccn1)c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
null
null
null
C-C Coupling
Heck terminal vinyl
868a29dcbb570a003a58cecf20153dd613d7e538ecd2b4cdca32c2d878e458b9
4b186811a4930853b446d93d9faa39b267bddb9ce0b8021bda5c5a3b2bc69f0b
C(=Cc1ccccn1)c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7].[#7;a:8]:[c:9]-[C:10]=[CH2;D1;+0:11]>>[#7;a:8]:[c:9]-[C:10]=[CH;D2;+0:11]-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7]
24
[{"value": 23.0, "product": "N1=C(C=CC=C1)C=CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 24.0, "product": "N1=C(C=CC=C1)C=CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
(R)-(−)-5′-Bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (150 mg, 0.5 mmol) was treated with 2-vinylpyridine (0.070 mL, 0.65 mmol) in the same way as described in example 16. Purification by flash chromatography through silica gel (eluting with ammoniated ether/methanol, 95:5 to 9:1), followed by ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Vinyl
null
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1ccncc1.c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
HBr
null
null
null
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C=Cc1ccccn1>>C(=Cc1ccccn1)c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-994c984101db47199f1323f5c8ec8cf2
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C#C[Si](C)(C)C>>C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
BrC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2.C[Si](C)(C)C#C.C(C)N(CC)CC>>C[Si](C#CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2)(C)C
Br[c:7]1[cH:8][n:9][c:10]2[c:11]([cH:12]1)[CH2:13][C@@:14]1([CH2:15][N:16]3[CH2:17][CH2:18][CH:19]1[CH2:20][CH2:21]3)[O:22]2.[CH3:1][Si:2]([CH3:3])([CH3:4])[C:5]#[CH:6]>>[CH3:1][Si:2]([CH3:3])([CH3:4])[C:5]#[C:6][c:7]1[cH:8][n:9][c:10]2[c:11]([cH:12]1)[CH2:13][C@@:14]1([CH2:15][N:16]3[CH2:17][CH2:18][CH:19]1[CH2:20][CH...
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C#C[Si](C)(C)C
C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
C(C)#N
C-C Coupling
Sonogashira alkyne_aryl halide
a3bd626b113853621b10067445273ac04b50534fbcc79a3a9cd99df3a91a853f
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4](:[#7;a:5]:[c:6]:1)-[#8:7].[C;D1;H3:8]-[#14:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C:12]#[CH;D1;+0:13]>>[#8:7]-[c:4]1:[#7;a:5]:[c:6]:[c;H0;D3;+0:1](-[C;H0;D2;+0:13]#[C:12]-[#14:9](-[C;D1;H3:8])(-[C;D1;H3:10])-[C;D1;H3:11]):[c:2]:[c:3]:1
90
[{"value": 90.0, "product": "C[Si](C#CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.0, "product": "C[Si](C#CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
(R)-(−)-5′-Bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine](295 mg, 1 mmol), trimethylsilylacetylene (0.355 mL, 2.5 mmol), tetrakis(triphenylphosphine)palladium (230 mg, 0.2 mmol), triethylamine (2 mL) and anhydrous acetonitrile (2 mL) were combined in a heavy-walled threaded glass tube containing a ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
HBr
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C(C)#N
100
null
Brc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2.C#C[Si](C)(C)C>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C(C)#N>C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7c05d78cea0d4b71b97f75b6203ea618
C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2>>C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
[F-].C(CCC)[N+](CCCC)(CCCC)CCCC.C[Si](C#CC=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2)(C)C>>C(#C)C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2
C[Si](C)(C)[C:1]#[C:2][c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C@@:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2>>[CH:1]#[C:2][c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C@@:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2
C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
null
null
O1CCCC1
Deprotection
TMS deprotection from alkyne
e85676bb81da384790c9c858d44f182cdd01e3a79f77f7a239fe38487234cb96
56d526d7c9cb1bd7bee4940e216a9b1dd4597fd025a186b8d6e4675d8f4db26b
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
C-[Si](-C)(-C)-[C;H0;D2;+0:1]#[C:2]-[c:3]:[c:4]:[#7;a:5]>>[#7;a:5]:[c:4]:[c:3]-[C:2]#[CH;D1;+0:1]
59
[{"value": 59.0, "product": "C(#C)C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.8, "product": "C(#C)C=1C=C2C(=NC1)O[C@@]1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Under an argon atmosphere, a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (1.3 mL, 1.3 mmol) was added at 0° C. to a solution of (R)-(−)-5′-(2-trimethylsilylethynyl)spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (265 mg, 0.85 mmol) in anhydrous tetrahydrofuran (5 mL), and stirred at ro...
10.6084/m9.figshare.5104873.v1
null
Alkyne.Silyl protective group
Alkyne
null
null
c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
Other
O1CCCC1
null
2
C[Si](C)(C)C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2>O1CCCC1>C#Cc1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7af79f3506d74c58ace3cefb3ebe7337
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1>>c1coc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.[Cl-].[Li+].C(CCC)[Sn](C=1OC=CC1)(CCCC)CCCC>>O1C(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[c:5]1[cH:6][n:7][c:8]2[c:9]([cH:10]1)[CH2:11][C:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c:4]1[o:3][cH:2][cH:1][cH:21]1>>[cH:1]1[cH:2][o:3][c:4](-[c:5]2[cH:6][n:7][c:8]3[c:9]([cH:10]2)[CH2:11][C:12]2([CH2:13][N:14]4[CH2:15][CH2:16][CH:17]2[CH2:18][CH2:19]...
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1
c1coc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
null
null
COCCOC.C(Cl)(Cl)Cl.CO
C-C Coupling
Stille reaction_aryl
cc39d7db0ec52886fc192130e358b3dc6844f4d8793ec13a4bc72377dc53431d
db27eeefac0475c6d74fa10b3167e95a61caaae74e8bbafd45892452c0c3d4d6
c1coc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4](:[#7;a:5]:[c:6]:1)-[#8:7].C-C-C-[CH2]-[Sn](-[CH2]-C-C-C)(-[CH2]-C-C-C)-[c;H0;D3;+0:8]1:[#8;a:9]:[c:10]:[c:11]:[c:12]:1>>[#8:7]-[c:4]1:[#7;a:5]:[c:6]:[c;H0;D3;+0:1](-[c;H0;D3;+0:8]2:[#8;a:9]:[c:10]:[c:11]:[c:12]:2):[c:2]:[c:3]:1
89.2
[{"value": 89.0, "product": "O1C(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 89.2, "product": "O1C(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution containing 5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (103.5 mg, 0.351 mmol), tris(dibenzylidineacetone)dipalladium (0) (14 mg, 0.015 mmol), tri(o-tolyl)phosphine (44.4 mg, 0.146 mmol), lithium chloride (62 mg, 1.46 mmol), and 2-(tri-n-butylstannyl)furan (0.17 g, 0.476 mmol) in 1,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
null
c1ccoc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccoc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccoc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr.Sn
COCCOC.C(Cl)(Cl)Cl.CO
null
null
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1>COCCOC.C(Cl)(Cl)Cl.CO>c1coc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1847636ca46e4936ac9734d1a061a8c8
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1cccnc1>>c1cncc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.[Cl-].[Li+].C(CCC)[Sn](C=1C=NC=CC1)(CCCC)CCCC>>N1=CC(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[c:6]1[cH:7][n:8][c:9]2[c:10]([cH:11]1)[CH2:12][C:13]1([CH2:14][N:15]3[CH2:16][CH2:17][CH:18]1[CH2:19][CH2:20]3)[O:21]2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c:5]1[cH:4][n:3][cH:2][cH:1][cH:22]1>>[cH:1]1[cH:2][n:3][cH:4][c:5](-[c:6]2[cH:7][n:8][c:9]3[c:10]([cH:11]2)[CH2:12][C:13]2([CH2:14][N:15]4[CH2:16][CH2:17][CH:18]2[C...
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1cccnc1
c1cncc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
null
null
COCCOC.C(Cl)(Cl)Cl.CO
C-C Coupling
Stille reaction_aryl
37d69164b75540068270b99151e8df9b79907e3444ec6d2ae6d0930ed34f1bc1
db27eeefac0475c6d74fa10b3167e95a61caaae74e8bbafd45892452c0c3d4d6
c1cncc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4](:[#7;a:5]:[c:6]:1)-[#8:7].C-C-C-[CH2]-[Sn](-[CH2]-C-C-C)(-[CH2]-C-C-C)-[c;H0;D3;+0:8]1:[c:9]:[c:10]:[c:11]:[#7;a:12]:[c:13]:1>>[#8:7]-[c:4]1:[#7;a:5]:[c:6]:[c;H0;D3;+0:1](-[c;H0;D3;+0:8]2:[c:9]:[c:10]:[c:11]:[#7;a:12]:[c:13]:2):[c:2]:[c:3]:1
37
[{"value": 37.0, "product": "N1=CC(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.0, "product": "N1=CC(=CC=C1)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution containing 5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (158 mg, 0.535 mmol), tris(dibenzylidineacetone)dipalladium (0) (23 mg, 0.025 mmol), tri(o-tolyl)phosphine (66 mg, 0.217 mmol), lithium chloride (99 mg, 2.34 mmol), and 3-(tri-n-butylstannyl)pyridine (0.3 ml, approx. 0.3 g, app...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
null
c1ccncc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccncc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccncc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr.Sn
COCCOC.C(Cl)(Cl)Cl.CO
null
null
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1cccnc1>COCCOC.C(Cl)(Cl)Cl.CO>c1cncc(-c2cnc3c(c2)CC2(CN4CCC2CC4)O3)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ada3d4d6b6934258b1891af4fddb420f
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.Cc1ccccc1P(c1ccccc1C)c1ccccc1C>>Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.[Cl-].[Li+].C[Sn](C)(C)C.C[Sn](C)(C)C>>CC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2.Cc1ccccc1P(c1ccccc1C)c1ccccc1[CH3:1]>>[CH3:1][c:2]1[cH:3][n:4][c:5]2[c:6]([cH:7]1)[CH2:8][C:9]1([CH2:10][N:11]3[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16]3)[O:17]2
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
CO.C(Cl)(Cl)Cl.COCCOCCOC
C-C Coupling
OtherReaction
006565e49c0251a32cb6e6adc643d7bcb3c08db70c255989d4adce0b2a1b79df
48892094855745f5c51f8910c27ce7c101e08ad3f9da2a58d5512e3d9c1b432f
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7].C-c1:c:c:c:c:c:1-P(-c1:c:c:c:c:c:1-C)-c1:c:c:c:c:c:1-[CH3;D1;+0:8]>>[#8:7]-[c:4]1:[#7;a:3]:[c:2]:[c;H0;D3;+0:1](-[CH3;D1;+0:8]):[c:6]:[c:5]:1
166.3
[{"value": 76.0, "product": "CC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 166.3, "product": "CC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
8
HOUR
A solution containing 5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (203 mg, 0.687 mmol), tris(dibenzylidineacetone)dipalladium (0) (33 mg, 0.036 mmol), tri(o-tolyl)phosphine (95 mg, 0.312 mmol), lithium chloride (241 mg, 5.69 mmol), and tetramethylstannane (1.0 ml, 1.3 g, 7.2 mmol) in 2-methox...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1.c1ccccc1.c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr
CO.C(Cl)(Cl)Cl.COCCOCCOC
100
8
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.Cc1ccccc1P(c1ccccc1C)c1ccccc1C>CO.C(Cl)(Cl)Cl.COCCOCCOC>Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9a4b5e2828164a48ac13b004ae0534ec
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCCC[C]([SnH3])=C(CCCC)CCCC>>C=Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
BrC=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2.C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.[Cl-].[Li+].C(CCC)C(=C(CCCC)CCCC)[SnH3]>>C(=C)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2
Br[c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2.CCCC[C]([SnH3])=[C:2](CCCC)[CH2:1]CCC>>[CH2:1]=[CH:2][c:3]1[cH:4][n:5][c:6]2[c:7]([cH:8]1)[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCCC[C]([SnH3])=C(CCCC)CCCC
C=Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
null
null
COCCOC.C(Cl)(Cl)Cl.CO
C-C Coupling
OtherReaction
18080a2f1bb3314985615348d358829f9d42deedef4105110c4aedd5fe47078a
345410b3017f34cc8d6f132ba8118ca6d91a18aa6891eed5be0d88d66e3cb480
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4](:[c:5]:[c:6]:1)-[#8:7].C-C-C-C-[C;H0;D3;+0:8](-[CH2;D2;+0:9]-C-C-C)=[C](-[SnH3])-C-C-C-C>>[#8:7]-[c:4]1:[#7;a:3]:[c:2]:[c;H0;D3;+0:1](-[CH;D2;+0:8]=[CH2;D1;+0:9]):[c:6]:[c:5]:1
186.9
[{"value": 76.0, "product": "C(=C)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 186.9, "product": "C(=C)C=1C=C2C(=NC1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution containing 5′-bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (150 mg, 0.508 mmol), tris(dibenzylidineacetone)dipalladium (0) (22 mg, 0.024 mmol), tri(o-tolyl)phosphine (63 mg, 0.206 mmol), lithium chloride (103 mg, 2.43 mmol), and tri-n-butylvinylstannane (188 mg, 0.592 mmol) in 1,2-dime...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
Vinyl
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HBr.Sn
COCCOC.C(Cl)(Cl)Cl.CO
null
null
Brc1cnc2c(c1)CC1(CN3CCC1CC3)O2.CCCC[C]([SnH3])=C(CCCC)CCCC>COCCOC.C(Cl)(Cl)Cl.CO>C=Cc1cnc2c(c1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-476390281feb45989a75873b005c2238
Clc1nccc2c1CC1(CN3CCC1CC3)O2>>c1cc2c(cn1)CC1(CN3CCC1CC3)O2
ClC1=NC=CC2=C1CC1(O2)CN2CCC1CC2>>O1C2(CC=3C=NC=CC31)CN3CCC2CC3
Cl[c:5]1[c:4]2[c:3]([cH:2][cH:1][n:6]1)[O:16][C:8]1([CH2:7]2)[CH2:9][N:10]2[CH2:11][CH2:12][CH:13]1[CH2:14][CH2:15]2>>[cH:1]1[cH:2][c:3]2[c:4]([cH:5][n:6]1)[CH2:7][C:8]1([CH2:9][N:10]3[CH2:11][CH2:12][CH:13]1[CH2:14][CH2:15]3)[O:16]2
Clc1nccc2c1CC1(CN3CCC1CC3)O2
c1cc2c(cn1)CC1(CN3CCC1CC3)O2
null
[Pd]
CO
Functional Group Interconversion
Aromatic dehalogenation
409aba9ea2f495f1cd7575e2525e8cdbab4e3d3dad539182b1a11a900dffed41
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1cc2c(cn1)CC1(CN3CCC1CC3)O2
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](:[c:5]-[#8:6])-[C:7]>>[#8:6]-[c:5]:[c:4](:[cH;D2;+0:1]:[#7;a:2]:[c:3])-[C:7]
104
[{"value": 104.0, "product": "O1C2(CC=3C=NC=CC31)CN3CCC2CC3", "details": "PERCENTYIELD", "is_desired": false}, {"value": 10.4, "product": "O1C2(CC=3C=NC=CC31)CN3CCC2CC3", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2.5
HOUR
The 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[3,2-c]pyridine] (125 mg or 5.0 mmol) from Example 33 was dissolved in 50 mL of anhydrous methanol, and 25 mg of 10% palladium on carbon was added. The bottle was placed on the Parr apparatus under hydrogen atmosphere and shaken for 2.5 hours. The Pd/C was remo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1cc2c(cn1)CC1(CN3CCC1CC3)O2
c1cc2c(cn1)CC1(CN3CCC1CC3)O2
c1cc2c(cn1)CC1(CN3CCC1CC3)O2
Other
[Pd].CO
null
2.5
Clc1nccc2c1CC1(CN3CCC1CC3)O2>[Pd].CO>c1cc2c(cn1)CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-36d6a0a3283b4c0cb8f1f21643e43c32
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.Sc1ccccc1>>c1ccc(Sc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
[H-].[Na+].ClC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2.C1(=CC=CC=C1)S.CO>>C1(=CC=CC=C1)SC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2
Cl[c:6]1[cH:7][cH:8][n:9][c:10]2[c:11]1[CH2:12][C:13]1([CH2:14][N:15]3[CH2:16][CH2:17][CH:18]1[CH2:19][CH2:20]3)[O:21]2.[cH:1]1[cH:2][cH:3][c:4]([SH:5])[cH:22][cH:23]1>>[cH:1]1[cH:2][cH:3][c:4]([S:5][c:6]2[cH:7][cH:8][n:9][c:10]3[c:11]2[CH2:12][C:13]2([CH2:14][N:15]4[CH2:16][CH2:17][CH:18]2[CH2:19][CH2:20]4)[O:21]3)[cH...
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.Sc1ccccc1
c1ccc(Sc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
null
null
O1CCOCC1.O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution thiol
4949d34a9b56fb58474d00eaedcaaefb0306d9d3b82d928dbda60c51edd0c176
97e4acce9b485bd597e518526ab4e9623782b1c9043b6e30dd257d386e3e5b01
c1ccc(Sc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]:1-[C:7])-[#8:8].[SH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[#8:8]-[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[S;H0;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:6]:1-[C:7]
52
[{"value": 52.0, "product": "C1(=CC=CC=C1)SC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.8, "product": "C1(=CC=CC=C1)SC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Sodium hydride (151 mg, 3.77 mmol) was added to a solution of 97 mg (0.387 mmol) of 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine], 0.40 mL (3.91 mmol) of thiophenol and 0.10 mL of methanol in 15 mL of dioxane, under a nitrogen atmosphere. The reaction was refluxed for 4 days, cooled to ambient...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic thiol
Monosulfide
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HCl
O1CCOCC1.O
null
null
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.Sc1ccccc1>O1CCOCC1.O>c1ccc(Sc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-72df2477f6824919b7517ebb41e06fbc
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCCN>>NCCNc1ccnc2c1CC1(CN3CCC1CC3)O2
ClC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2.C(CN)N>>NCCNC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2
Cl[c:5]1[cH:6][cH:7][n:8][c:9]2[c:10]1[CH2:11][C:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2.[NH2:1][CH2:2][CH2:3][NH2:4]>>[NH2:1][CH2:2][CH2:3][NH:4][c:5]1[cH:6][cH:7][n:8][c:9]2[c:10]1[CH2:11][C:12]1([CH2:13][N:14]3[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19]3)[O:20]2
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCCN
NCCNc1ccnc2c1CC1(CN3CCC1CC3)O2
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
134857cf068afab7db9d749865c145d72b51c63b5036fd443b040ea288986bd5
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]:1-[C:7])-[#8:8].[C:9]-[C:10]-[NH2;D1;+0:11]>>[#8:8]-[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:10]-[C:9]):[c:6]:1-[C:7]
null
[]
null
null
4
DAY
A solution of 74 mg (0.295 mmol) of 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] in 10 mL of ethylenediamine was heated to reflux under a nitrogen atmosphere and stirred for 4 days. Upon cooling to ambient temperature, the solvent was removed in vacuo. The residue was dissolved in 20 mL of sa...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HCl
null
null
96
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCCN>>NCCNc1ccnc2c1CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-80bc069d916e4770895774d36f8b9ca7
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCc1ccccc1>>c1ccc(CNc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
ClC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2.C(C1=CC=CC=C1)N.C([O-])([O-])=O.[Na+].[Na+]>>C1(=CC=CC=C1)CNC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2
Cl[c:7]1[cH:8][cH:9][n:10][c:11]2[c:12]1[CH2:13][C:14]1([CH2:15][N:16]3[CH2:17][CH2:18][CH:19]1[CH2:20][CH2:21]3)[O:22]2.[cH:1]1[cH:2][cH:3][c:4]([CH2:5][NH2:6])[cH:23][cH:24]1>>[cH:1]1[cH:2][cH:3][c:4]([CH2:5][NH:6][c:7]2[cH:8][cH:9][n:10][c:11]3[c:12]2[CH2:13][C:14]2([CH2:15][N:16]4[CH2:17][CH2:18][CH:19]2[CH2:20][CH...
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCc1ccccc1
c1ccc(CNc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
null
null
O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
134857cf068afab7db9d749865c145d72b51c63b5036fd443b040ea288986bd5
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(CNc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]:1-[C:7])-[#8:8].[NH2;D1;+0:9]-[C:10]-[c:11]>>[#8:8]-[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[C:10]-[c:11]):[c:6]:1-[C:7]
34
[{"value": 34.0, "product": "C1(=CC=CC=C1)CNC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A solution of 97 mg (0.387 mmol) of 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] in 5 mL of benzylamine was heated to reflux under a nitrogen atmosphere and stirred for 18 hours. Upon cooling to ambient temperature, the diluted with 40 mL of water, basicified with 2 mL of saturated aqueous so...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1ccccc1.c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HCl
O
null
18
Clc1ccnc2c1CC1(CN3CCC1CC3)O2.NCc1ccccc1>O>c1ccc(CNc2ccnc3c2CC2(CN4CCC2CC4)O3)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bf751cda76f642388b220e1284545732
CN.Clc1ccnc2c1CC1(CN3CCC1CC3)O2>>CNc1ccnc2c1CC1(CN3CCC1CC3)O2
ClC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2.CN>>CNC1=C2C(=NC=C1)OC1(C2)CN2CCC1CC2
[CH3:1][NH2:2].Cl[c:3]1[cH:4][cH:5][n:6][c:7]2[c:8]1[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2>>[CH3:1][NH:2][c:3]1[cH:4][cH:5][n:6][c:7]2[c:8]1[CH2:9][C:10]1([CH2:11][N:12]3[CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]3)[O:18]2
CN.Clc1ccnc2c1CC1(CN3CCC1CC3)O2
CNc1ccnc2c1CC1(CN3CCC1CC3)O2
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
134857cf068afab7db9d749865c145d72b51c63b5036fd443b040ea288986bd5
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]:1-[C:7])-[#8:8].[C;D1;H3:9]-[NH2;D1;+0:10]>>[#8:8]-[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C;D1;H3:9]):[c:6]:1-[C:7]
null
[]
null
null
8
HOUR
A solution of 151 mg (0.60 mmol) of 4′-chlorospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] in 25 mL of 40% aqueous methylamine was heated to 175° C. in a steel bomb for 18 hours, then cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in 10 mL of ethanol containing 0.4 m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
c1cnc2c(c1)CC1(CN3CCC1CC3)O2
HCl
null
null
8
CN.Clc1ccnc2c1CC1(CN3CCC1CC3)O2>>CNc1ccnc2c1CC1(CN3CCC1CC3)O2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-519cad054db84e83af78a0efbeb0aa4f
CC(C)(C)OC(=O)[C@@H]1C[C@@H](Oc2ccc(Cl)c3c2C2(CCCCC2)NC(=O)N3)C1.O>>CC(=O)O.O=C1Nc2c(Cl)ccc(O[C@@H]3C[C@@H](C(=O)O)C3)c2C2(CCCCC2)N1
C(C)(C)(C)OC(=O)[C@@H]1C[C@H](C1)OC1=C2C3(NC(NC2=C(C=C1)Cl)=O)CCCCC3.Br.O>>C(C)(=O)O.ClC=1C=CC(=C2C3(NC(NC12)=O)CCCCC3)O[C@@H]3C[C@H](C3)C(=O)O
C[C:2](C)([CH3:1])[O:20][C:18]([C@H:17]1[CH2:16][C@H:15]([O:14][c:13]2[cH:12][cH:11][c:9]([Cl:10])[c:8]3[c:22]2[C:23]2([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)[NH:29][C:6](=[O:5])[NH:7]3)[CH2:21]1)=[O:19].[OH2:3]>>[CH3:1][C:2](=[O:3])[OH:4].[O:5]=[C:6]1[NH:7][c:8]2[c:9]([Cl:10])[cH:11][cH:12][c:13]([O:14][C@H:15]3[CH...
CC(C)(C)OC(=O)[C@@H]1C[C@@H](Oc2ccc(Cl)c3c2C2(CCCCC2)NC(=O)N3)C1.O
CC(=O)O.O=C1Nc2c(Cl)ccc(O[C@@H]3C[C@@H](C(=O)O)C3)c2C2(CCCCC2)N1
null
null
C(C)(=O)O
Acylation
OtherReaction
c226912d3365eb5e64be0dac8784ffb753b865db0f0adba41564a4f98ca8828d
c129c2d4bf8d003b6d5cd4342bab040c800a372eb4262218bb5ae9fce91f728a
O=C1Nc2cccc(OC3CCC3)c2C2(CCCCC2)N1
C-[C;H0;D4;+0:1](-C)(-[C;D1;H3:2])-[O;H0;D2;+0:3]-[C:4](-[C:5])=[O;D1;H0:6].[OH2;D0;+0:7]>>[C;D1;H3:2]-[C;H0;D3;+0:1](-[O;D1;H1:8])=[O;H0;D1;+0:7].[C:5]-[C:4](=[O;D1;H0:6])-[OH;D1;+0:3]
null
[]
60
CELSIUS
30
MINUTE
The product of step (a) (207 g, 0.492 mol) was slurried in acetic acid (3100 ml) and heated to 60° C. 48% Hydrobromic acid (4.93 mol) was added dropwise keeping the temperature at 60° C. The solution was stirred at 60° C. for 30 minutes. Water (700 ml) was added dropwise keeping the temperature above 55° C. The slurry ...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid.Carboxylic acid
null
null
C1CCC1.c1ccc2c(c1)NCNC21CCCCC1
Other
C(C)(=O)O
60
0.5
CC(C)(C)OC(=O)[C@@H]1C[C@@H](Oc2ccc(Cl)c3c2C2(CCCCC2)NC(=O)N3)C1.O>C(C)(=O)O>CC(=O)O.O=C1Nc2c(Cl)ccc(O[C@@H]3C[C@@H](C(=O)O)C3)c2C2(CCCCC2)N1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d7985848d23b4f51ade2ab9ba36c2753
C=CCOCc1ccccc1.O=C(Cl)C(Cl)(Cl)Cl>>O=C1CC(COCc2ccccc2)C1(Cl)Cl
COCCOC.C(C1=CC=CC=C1)OCC=C.ClC(C(=O)Cl)(Cl)Cl.COCCOC>>C(C1=CC=CC=C1)OCC1C(C(C1)=O)(Cl)Cl
[CH2:3]=[CH:4][CH2:5][O:6][CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1.Cl[C:2](=[O:1])[C:14](Cl)([Cl:15])[Cl:16]>>[O:1]=[C:2]1[CH2:3][CH:4]([CH2:5][O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[C:14]1([Cl:15])[Cl:16]
C=CCOCc1ccccc1.O=C(Cl)C(Cl)(Cl)Cl
O=C1CC(COCc2ccccc2)C1(Cl)Cl
null
[Zn].S(=O)(=O)([O-])[O-].[Cu+2]
O.C(C)OCC
C-C Coupling
OtherReaction
6abbed25a72e027e758a3223966873406862851af82e412acd5d1f8b8bf66b2e
57d4700a378a1cafce563da9f5eedffe4be9c91366df44aa034da7d71823d308
O=C1CC(COCc2ccccc2)C1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D4;+0:3](-Cl)(-[Cl;D1;H0:4])-[Cl;D1;H0:5].[#8:6]-[C:7]-[CH;D2;+0:8]=[CH2;D1;+0:9]>>[#8:6]-[C:7]-[CH;D3;+0:8]1-[CH2;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D4;+0:3]-1(-[Cl;D1;H0:4])-[Cl;D1;H0:5]
91
[{"value": 91.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.0, "product": null, "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
Zinc dust (6.54 g, 0.1 mol) was suspended in water (30 ml) and argon bubbled through the suspension for 15 minutes before the addition of copper (II) sulphate (780 mg, 3.1 mmol). The reaction mixture was stirred at room temperature, under argon for 30 minutes. The mixture was filtered under a stream of argon and the so...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Trichloro group.Allyl
Tertiary halide.Tertiary halide.Ketone
null
C1CCC1
C1CCC1.c1ccccc1
Other
[Zn].S(=O)(=O)([O-])[O-].[Cu+2].O.C(C)OCC
null
0.5
C=CCOCc1ccccc1.O=C(Cl)C(Cl)(Cl)Cl>[Zn].S(=O)(=O)([O-])[O-].[Cu+2].O.C(C)OCC>O=C1CC(COCc2ccccc2)C1(Cl)Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e1b73198fb504a57abdf39bd7fa3a0f2
O=C(n1ccnc1)n1ccnc1.OCc1ccccc1>>C=C1CC(C(=O)OCc2ccccc2)C1
C(=O)(N1C=NC=C1)N1C=NC=C1.C(C1=CC=CC=C1)O>>C(C1=CC=CC=C1)OC(=O)C1CC(C1)=C
c1n[cH:2][cH:1]n1[C:5](n1[cH:3]n[cH:15][cH:4]1)=[O:6].[OH:7][CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[CH2:1]=[C:2]1[CH2:3][CH:4]([C:5](=[O:6])[O:7][CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[CH2:15]1
O=C(n1ccnc1)n1ccnc1.OCc1ccccc1
C=C1CC(C(=O)OCc2ccccc2)C1
null
null
C(C)(=O)OCC.C(C)OCC
Acylation
OtherReaction
0903b1780b1860613067b6a279fd787affc985e3bf5d11f9fd80b72f9028cbc9
88e97d733db5d6c9928ade3a394c136a01dda34d71b6a4f75cbc78ddb2d31fc0
C=C1CC(C(=O)OCc2ccccc2)C1
[O;D1;H0:1]=[C;H0;D3;+0:2](-n1:[cH;D2;+0:3]:n:[cH;D2;+0:4]:[cH;D2;+0:5]:1)-n1:[cH;D2;+0:6]:[cH;D2;+0:7]:n:c:1.[OH;D1;+0:8]-[C:9]-[c:10]>>[CH2;D1;+0:6]=[C;H0;D3;+0:7]1-[CH2;D2;+0:4]-[CH;D3;+0:5](-[C;H0;D3;+0:2](=[O;D1;H0:1])-[O;H0;D2;+0:8]-[C:9]-[c:10])-[CH2;D2;+0:3]-1
115.2
[{"value": 69.0, "product": "C(C1=CC=CC=C1)OC(=O)C1CC(C1)=C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 115.2, "product": "C(C1=CC=CC=C1)OC(=O)C1CC(C1)=C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
A suspension of 1,1′-carbonyldiimidazole (1.59 g, 9.81 mmol) in ethyl acetate (5 ml) was added in portions to a solution of the product of Preparation 12 (1 g, 8.9 mmol) in ethyl acetate (5 ml). Gentle effervescence was observed. The mixture was stirred at room temperature for about 1.5 hours, benzyl alcohol (1.11 ml, ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Ester.Vinyl
c1c[nH]cn1.c1c[nH]cn1
C1CCC1
C1CCC1.c1ccccc1
Other
C(C)(=O)OCC.C(C)OCC
null
1.5
O=C(n1ccnc1)n1ccnc1.OCc1ccccc1>C(C)(=O)OCC.C(C)OCC>C=C1CC(C(=O)OCc2ccccc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2ef08f14722d41c18085c414992dcd0f
COC(=O)C1(C(=O)OC)CCC1>>COC(=O)C1(CO)CCC1
COC(=O)C1(CCC1)C(=O)OC.[H-].C(C)(C)(C)O[Al](OC(C)(C)C)OC(C)(C)C.[Li+]>>COC(=O)C1(CCC1)CO
CO[C:6]([C:5]1([C:3]([O:2][CH3:1])=[O:4])[CH2:8][CH2:9][CH2:10]1)=[O:7]>>[CH3:1][O:2][C:3](=[O:4])[C:5]1([CH2:6][OH:7])[CH2:8][CH2:9][CH2:10]1
COC(=O)C1(C(=O)OC)CCC1
COC(=O)C1(CO)CCC1
null
null
O1CCCC1.[Cl-].[NH4+]
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C1CCC1
C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3](-[C:4](=[O;D1;H0:5])-[#8:6]-[C;D1;H3:7])(-[C:8])-[C:9]>>[C:8]-[C:3](-[CH2;D2;+0:1]-[OH;D1;+0:2])(-[C:4](=[O;D1;H0:5])-[#8:6]-[C;D1;H3:7])-[C:9]
107.6
[{"value": 107.6, "product": "COC(=O)C1(CCC1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
To a solution of 1,1-cyclobutanedicarboxylic acid dimethyl ester (available from Lancaster Synthesis Ltd, UK) (2.0 g, 11.6 mmol) in tetrahydrofuran (20 ml) at room temperature was added lithium tri-tert-butoxyaluminium hydride (25.5 ml of a 1M solution in tetrahydrofuran, 25.5 mmol) dropwise over 10 minutes. The reacti...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1CCC1
Other
O1CCCC1.[Cl-].[NH4+]
null
18
COC(=O)C1(C(=O)OC)CCC1>O1CCCC1.[Cl-].[NH4+]>COC(=O)C1(CO)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-720b28c5db0f4890a338ebe8e375c616
COc1ccc(Cl)c(N)c1.N#C[O-]>>COc1ccc(Cl)c(NC(N)=O)c1
Cl.ClC1=C(N)C=C(C=C1)OC.C(C)(=O)O.[O-]C#N.[K+]>>ClC1=C(C=C(C=C1)OC)NC(=O)N
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([NH2:9])[cH:13]1.[C:10](#[N:11])[O-:12]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([NH:9][C:10]([NH2:11])=[O:12])[cH:13]1
COc1ccc(Cl)c(N)c1.N#C[O-]
COc1ccc(Cl)c(NC(N)=O)c1
null
null
O
Acylation
OtherReaction
f8798d1193af6f9b314ac8855e814716b90ff3758bcfa29778cc632fcaa83b7a
5efe06db19c806d9e9798893351dc14c0cc48f1e8f8c857f54c6171e86c96a1b
c1ccccc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[O-;H0;D1:3].[NH2;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[NH;D2;+0:4]-[c:5](:[c:6]):[c:7]
81.1
[{"value": 81.0, "product": "ClC1=C(C=C(C=C1)OC)NC(=O)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.1, "product": "ClC1=C(C=C(C=C1)OC)NC(=O)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
30
CELSIUS
1
HOUR
2-Chloro-5-methoxyaniline hydrochloride (26 g, 134 mmol) was added to acetic acid (117 ml) and water (13 ml). The slurry was warmed to 30° C. A solution of potassium cyanate (13 g, 161 mmol) in water (104 ml) was added dropwise. After 1 hour at 40° C., the reaction was cooled to 20° C., filtered and washed with water (...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
Urea
null
null
c1ccccc1
null
O
30
1
COc1ccc(Cl)c(N)c1.N#C[O-]>O>COc1ccc(Cl)c(NC(N)=O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4c3711d37de04af6b2801673c3f820ea
COC(=O)C=C1CC2CCC(C1)N2C.[Li][c]1cccs1>>CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[NH4+].[OH-]
COC(C=C1CC2CCC(C1)N2C)=O.S1C(=CC=C1)[Li]>>[NH4+].[OH-].CN1C2CC(CC1CC2)=CC(O)(C=2SC=CC2)C=2SC=CC2
[CH3:1][N:2]1[CH:3]2[CH2:4][CH2:5][CH:6]1[CH2:7][C:8](=[CH:9][C:10](=[O:11])[O:24][CH3:12])[CH2:22]2.[Li][c:17]1[s:16][cH:15][cH:14][cH:18]1>>[CH3:1][N:2]1[CH:3]2[CH2:4][CH2:5][CH:6]1[CH2:7][C:8](=[CH:9][C:10]([OH:11])([c:12]1[cH:13][cH:14][cH:15][s:16]1)[c:17]1[cH:18][cH:19][cH:20][s:21]1)[CH2:22]2.[NH4+:23].[OH-:24]
COC(=O)C=C1CC2CCC(C1)N2C.[Li][c]1cccs1
CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[NH4+].[OH-]
null
null
[NH4+].[Cl-].C1CCOC1
Aromatic Heterocycle Formation
OtherReaction
cb5bcc5cf66f08b5117f8fd57d6c931fa0eaf03660bb28e0f4a73bc046a47144
01d389a1ef988a5ea0b552ba0951ad0e66e36786c8a2ad92712297c57283a47f
C(=C1CC2CCC(C1)N2)C(c1cccs1)c1cccs1
[C:1]-[C:2](=[C:3]-[C;H0;D3;+0:4](=[O;H0;D1;+0:5])-[O;H0;D2;+0:6]-[CH3;D1;+0:7])-[C:8].[Li]-[c;H0;D3;+0:9]1:[cH;D2;+0:10]:[cH;D2;+0:11]:[c:12]:[s;H0;D2;+0:13]:1>>[C:1]-[C:2](=[C:3]-[C;H0;D4;+0:4](-[OH;D1;+0:5])(-[c;H0;D3;+0:7]1:[c:14]:[cH;D2;+0:11]:[c:12]:[s;H0;D2;+0:13]:1)-[c;H0;D3;+0:9]1:[#16;a:15]:[c:16]:[c:17]:[cH;...
78.1
[{"value": 2.0, "product": "[NH4+].[OH-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.0, "product": "CN1C2CC(CC1CC2)=CC(O)(C=2SC=CC2)C=2SC=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.1, "product": "CN1C2CC(CC1CC2)=CC(O)(C=2SC=CC2)C=2SC=CC2", "details": "CALCULATEDPERCENTYIELD"...
null
null
8
HOUR
A solution of (8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-acetic acid methyl ester (200 mg, 1.02 mmol) in THF (3 mL) was mixed with 2-thienyllithium (2.02 mL, 1.0 M in THF, 2.02 mmol). The mixture was stirred overnight at r.t., diluted with saturated NH4Cl aqueous solution (20 mL) and extracted with EtOAc. The combine...
10.6084/m9.figshare.5104873.v1
null
Ester.Aryl lithium
Tertiary alcohol
c1ccsc1
c1ccsc1.c1ccsc1
C1CC2CCC(C1)[NH]2.c1ccsc1.c1ccsc1
Li
[NH4+].[Cl-].C1CCOC1
null
8
COC(=O)C=C1CC2CCC(C1)N2C.[Li][c]1cccs1>[NH4+].[Cl-].C1CCOC1>CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[NH4+].[OH-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-514af9cf31ba4887b680bf006359b56b
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][CH2]c1ccccc1>>CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2
COC(C=C1CC2CCC(C1)N2C)=O.C(C1=CC=CC=C1)[Mg]Cl>>C(C1=CC=CC=C1)C(C=C1CC2CCC(C1)N2C)(CC2=CC=CC=C2)O
O([C:10]([CH:9]=[C:8]1[CH2:7][CH:6]2[N:2]([CH3:1])[CH:3]([CH2:4][CH2:5]2)[CH2:26]1)=[O:11])[CH3:19].[Cl][Mg][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][N:2]1[CH:3]2[CH2:4][CH2:5][CH:6]1[CH2:7][C:8](=[CH:9][C:10]([OH:11])([CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH2:19][c:20]1[cH:21][cH:22][...
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][CH2]c1ccccc1
CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2
null
null
null
C-C Coupling
OtherReaction
d9cfd08fb0ae0e08e2abfc9e2e9717581ce24fe474620e538d84c93665d152c2
0b91bc36d63c570fba02035c23fdcf278e8164647420394f29330caa2ac0d989
C(=C1CC2CCC(C1)N2)C(Cc1ccccc1)Cc1ccccc1
[C:1]-[C:2](=[C:3]-[C;H0;D3;+0:4](=[O;H0;D1;+0:5])-O-[CH3;D1;+0:6])-[C:7].[Cl]-[Mg]-[CH2;D2;+0:8]-[c:9](:[c:10]):[c:11]>>[C:1]-[C:2](=[C:3]-[C;H0;D4;+0:4](-[OH;D1;+0:5])(-[CH2;D2;+0:8]-[c:9](:[c:10]):[c:11])-[CH2;D2;+0:6]-[c:12](:[c:13]):[c:14])-[C:7]
31
[{"value": 31.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from (8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-acetic acid methyl ester and benzylmagnesium chloride by following the experimental procedures in Example 1 (31% yield): LCMS (ES) m/z 348 (M+H)+; 1H-NMR(CDCl3) δ 0.90 (m, 1H), 1.25 (m, 1H), 1.61 (m, 1H), 1.81 (m, 3H), 2.20 (s, 3H), 2.40 ...
10.6084/m9.figshare.5104873.v1
null
Magnesium halide.Ester
Tertiary alcohol
null
c1ccccc1
C1CC2CCC(C1)[NH]2.c1ccccc1.c1ccccc1
Mg
null
null
null
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][CH2]c1ccccc1>>CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-98bcc45c4c96452387c7b29229477e69
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][c]1ccccc1>>CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2
COC(C=C1CC2CCC(C1)N2C)=O.C1(=CC=CC=C1)[Mg]Cl>>CN1C2CC(CC1CC2)=CC(O)(C2=CC=CC=C2)C2=CC=CC=C2
O([C:10]([CH:9]=[C:8]1[CH2:7][CH:14]2[N:2]([CH3:1])[CH:3]([CH2:4][CH2:15]2)[CH2:24]1)=[O:11])[CH3:17].[Cl][Mg][c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1>>[CH3:1][N:2]1[CH:3]2[CH2:4][CH2:5][CH:6]1[CH2:7][C:8](=[CH:9][C:10]([OH:11])([c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1)[c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1)...
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][c]1ccccc1
CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2
null
null
null
Aromatic Heterocycle Formation
OtherReaction
109882035845b38cc5dc16781c120787dd673fe69b2cc3aa6c23500e4abea651
86699f3430ab47d59e6b5700fdac59e8de3d70ed63f18e2ca2dc71019642ab75
C(=C1CC2CCC(C1)N2)C(c1ccccc1)c1ccccc1
[C;D1;H3:1]-[N;H0;D3;+0:2]1-[C:3]2-[C:4]-[C:5](=[C:6]-[C;H0;D3;+0:7](=[O;H0;D1;+0:8])-O-[CH3;D1;+0:9])-[CH2;D2;+0:10]-[CH;D3;+0:11]-1-[CH2;D2;+0:12]-[CH2;D2;+0:13]-2.[Cl]-[Mg]-[c;H0;D3;+0:14](:[c:15]:[c:16]):[c:17]:[c:18]>>[C;D1;H3:1]-[N;H0;D3;+0:2]1-[C:3]2-[C:4]-[C:5](=[C:6]-[C;H0;D4;+0:7](-[OH;D1;+0:8])(-[c:19]3:[c:2...
44
[{"value": 44.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from (8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-acetic acid methyl ester and phenylmagnesium chloride by following the experimental procedures in Example 1 (44% yield): LCMS (ES) m/z 320 (M+H)+; 1H-NMR(CDCl3) δ 1.20 (m, 1H), 1.54 (m, 1H), 1.70 (m, 1H), 1.77 (m, 1H), 1.93 (m, 1H), 2.04 ...
10.6084/m9.figshare.5104873.v1
null
Magnesium halide.Ester.Tertiary amine
Tertiary alcohol.Tertiary amine
C1CC2CCC(C1)[NH]2.c1ccccc1
C1CC2CCC(C1)[NH]2.c1ccccc1.c1ccccc1
C1CC2CCC(C1)[NH]2.c1ccccc1.c1ccccc1
Mg
null
null
null
COC(=O)C=C1CC2CCC(C1)N2C.[Cl][Mg][c]1ccccc1>>CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9dae07e19343494ca2fe90fa06300d88
CI.CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2>>C[N+]1(C)C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[I-]
CN1C2CC(CC1CC2)=CC(O)(C=2SC=CC2)C=2SC=CC2.CI.C(=O)([O-])[O-].[K+].[K+]>>[I-].OC(C=C1CC2CCC(C1)[N+]2(C)C)(C=2SC=CC2)C=2SC=CC2
[CH3:1][I:24].[N:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([c:13]1[cH:14][cH:15][cH:16][s:17]1)[c:18]1[cH:19][cH:20][cH:21][s:22]1)[CH2:23]2>>[CH3:1][N+:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([c:13]1[cH:14][cH:15][cH:16][s:17]1)[c:18]1[cH:19][cH:2...
CI.CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2
C[N+]1(C)C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[I-]
null
null
CC#N.C(Cl)Cl
Functional Group Interconversion
OtherReaction
16315b4d9ba4ae696eb90959c43c2d29df91c9d68f104b046ab1eda58093348c
5a8d30abc7481f1c446ec3891ae2e6d38df9cf7a08165b843f1d24fc50c4b9cd
C(=C1CC2CCC(C1)[NH2+]2)C(c1cccs1)c1cccs1
[CH3;D1;+0:1]-[I;H0;D1;+0:2].[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N;H0;D3;+0:11]-2-[C;D1;H3:12]>>[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N+;H0;D4:11]-2(-[C;D1;H3:12])-[CH3;D1;+0:1].[I-;H0;D0:2]
96
[{"value": 96.0, "product": "[I-].OC(C=C1CC2CCC(C1)[N+]2(C)C)(C=2SC=CC2)C=2SC=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.4, "product": "[I-].OC(C=C1CC2CCC(C1)[N+]2(C)C)(C=2SC=CC2)C=2SC=CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of 2-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-1,1-di-thiophen-2-yl-ethanol (10 mg, 0.03 mmol) in CH3CN (1 mL) and CH2Cl2 (0.5 mL) was mixed with methyliodide (0.038 mL, 0.6 mmol) and K2CO3 (0.1 g, 0.7 mmol). The mixture was stirred overnight at r.t. and filtered. Separation via a reverse-phase HPLC then ...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
null
C1CC2CCC(C1)[NH]2
C1CC2CCC(C1)[NH+]2
C1CC2CCC(C1)[NH+]2.c1ccsc1.c1ccsc1
null
CC#N.C(Cl)Cl
null
8
CI.CN1C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2>CC#N.C(Cl)Cl>C[N+]1(C)C2CCC1CC(=CC(O)(c1cccs1)c1cccs1)C2.[I-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-587843cf6e104bbc853af7ec7ec04ed5
CI.CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2>>C[N+]1(C)C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2.[I-]
C(C1=CC=CC=C1)C(C=C1CC2CCC(C1)N2C)(CC2=CC=CC=C2)O.CI>>[I-].C(C1=CC=CC=C1)C(C=C1CC2CCC(C1)[N+]2(C)C)(CC2=CC=CC=C2)O
[CH3:1][I:28].[N:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1)[CH2:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1)[CH2:27]2>>[CH3:1][N+:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([CH2:13][c:14]1[cH:15][...
CI.CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2
C[N+]1(C)C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2.[I-]
null
null
null
Functional Group Interconversion
OtherReaction
16315b4d9ba4ae696eb90959c43c2d29df91c9d68f104b046ab1eda58093348c
5a8d30abc7481f1c446ec3891ae2e6d38df9cf7a08165b843f1d24fc50c4b9cd
C(=C1CC2CCC(C1)[NH2+]2)C(Cc1ccccc1)Cc1ccccc1
[CH3;D1;+0:1]-[I;H0;D1;+0:2].[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N;H0;D3;+0:11]-2-[C;D1;H3:12]>>[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N+;H0;D4:11]-2(-[C;D1;H3:12])-[CH3;D1;+0:1].[I-;H0;D0:2]
85
[{"value": 85.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from 2-benzyl-1-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-3-phenyl-propan-2-ol and methyliodide by following the experimental procedures in Example 4 (85% yield): LCMS (ES) m/z 346 (M+H)+; 1H-NMR(CDCl3) δ 0.80 (m, 1H), 1.48 (m, 1H), 1.84 (m, 1H), 1.99 (m, 1H), 2.09 (m, 2H), 2.87 (m, 1...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
null
C1CC2CCC(C1)[NH]2
C1CC2CCC(C1)[NH+]2
C1CC2CCC(C1)[NH+]2.c1ccccc1.c1ccccc1
null
null
null
null
CI.CN1C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2>>C[N+]1(C)C2CCC1CC(=CC(O)(Cc1ccccc1)Cc1ccccc1)C2.[I-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2c9484adda5b465bba157e391c1695b8
CI.CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2>>C[N+]1(C)C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2.[I-]
CN1C2CC(CC1CC2)=CC(O)(C2=CC=CC=C2)C2=CC=CC=C2.CI>>[I-].OC(C=C1CC2CCC(C1)[N+]2(C)C)(C2=CC=CC=C2)C2=CC=CC=C2
[CH3:1][I:26].[N:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1)[CH2:25]2>>[CH3:1][N+:2]1([CH3:3])[CH:4]2[CH2:5][CH2:6][CH:7]1[CH2:8][C:9](=[CH:10][C:11]([OH:12])([c:13]1[cH:14][cH:15][cH:16][cH:17][cH:...
CI.CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2
C[N+]1(C)C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2.[I-]
null
null
null
Functional Group Interconversion
OtherReaction
16315b4d9ba4ae696eb90959c43c2d29df91c9d68f104b046ab1eda58093348c
5a8d30abc7481f1c446ec3891ae2e6d38df9cf7a08165b843f1d24fc50c4b9cd
C(=C1CC2CCC(C1)[NH2+]2)C(c1ccccc1)c1ccccc1
[CH3;D1;+0:1]-[I;H0;D1;+0:2].[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N;H0;D3;+0:11]-2-[C;D1;H3:12]>>[C:3]=[C:4]1-[C:5]-[C:6]2-[C:7]-[C:8]-[C:9](-[C:10]-1)-[N+;H0;D4:11]-2(-[C;D1;H3:12])-[CH3;D1;+0:1].[I-;H0;D0:2]
67
[{"value": 67.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from 2-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-1,1-diphenyl-ethanol and methyliodide by following the experimental procedures in Example 4 (67% yield): LCMS (ES) m/z 334 (M+H)+; 1H-NMR(CDCl3) δ 1.50 (m, 1H), 1.98 (m, 1H), 2.11 (m, 1H), 2.35 (m, 2H), 2.87 (m, 1H), 2.96 (m, 1H), 3.23 ...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
null
C1CC2CCC(C1)[NH]2
C1CC2CCC(C1)[NH+]2
C1CC2CCC(C1)[NH+]2.c1ccccc1.c1ccccc1
null
null
null
null
CI.CN1C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2>>C[N+]1(C)C2CCC1CC(=CC(O)(c1ccccc1)c1ccccc1)C2.[I-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7891fb96a57840c0b1b30def96b4804c
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Cl)nc3ncnn3c2Cl)c(F)c1>>C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)Cl)N=CN2.Cl.FC([C@H](C)N)(F)F.C(C)(C)N(C(C)C)CC>>ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2
[CH3:1][C@H:2]([NH2:3])[C:23]([F:24])([F:25])[F:26].Cl[c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([F:11])[cH:12][c:13]2[F:14])[c:15]([Cl:16])[n:17][c:18]2[n:19][cH:20][n:21][n:22]12>>[CH3:1][C@H:2]([NH:3][c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([F:11])[cH:12][c:13]2[F:14])[c:15]([Cl:16])[n:17][c:18]2[n:19][cH:20][n:...
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Cl)nc3ncnn3c2Cl)c(F)c1
C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
null
null
CN(C=O)C.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
680ce65987443e27ed1de90a7e61da2b858a904becdcfebe764b8f0fdb130b5c
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2cnc3ncnn3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]2:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]:2:[#7;a:7]:[c:8](-[Cl;D1;H0:9]):[c:10]:1-[c:11].[C;D1;H3:12]-[C:13](-[NH2;D1;+0:14])-[C:15](-[F;D1;H0:16])(-[F;D1;H0:17])-[F;D1;H0:18]>>[C;D1;H3:12]-[C:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]1:[#7;a:2]2:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]:2:[#7;a:7]:[c:8](-[Cl;D1;H0:9]):[c...
95.7
[{"value": 95.7, "product": "ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
13
HOUR
A mixture of 5,7-dichloro-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine (3.0 g, 9.4 mmol), (1S)-2,2,2-trifluoro-1-methylethylamine hydrogen chloride (4.2 g, 28.2 mmol), and N,N-diisopropylethylamine (4.9 mL, 28.2 mmol) in 100 mL of N,N-dimethylformamide is stirred at room temperature under nitrogen atmosphe...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2ncnn2c1
c1cnc2ncnn2c1
c1ccccc1.c1cnc2ncnn2c1
HCl
CN(C=O)C.C(C)(=O)OCC
null
13
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Cl)nc3ncnn3c2Cl)c(F)c1>CN(C=O)C.C(C)(=O)OCC>C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-421dbdeda10342f28090350c0dc828e7
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F>>C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
O.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2.CN(CCCO)C.[H-].[Na+]>>ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCN(C)C)F)N[C@H](C(F)(F)F)C)N=CN2
[OH:11][CH2:12][CH2:13][CH2:14][N:15]([CH3:16])[CH3:17].F[c:10]1[cH:9][c:7]([F:8])[c:6](-[c:5]2[c:4]([NH:3][C@@H:2]([CH3:1])[C:29]([F:30])([F:31])[F:32])[n:28]3[c:24]([n:23][c:21]2[Cl:22])[n:25][cH:26][n:27]3)[c:19]([F:20])[cH:18]1>>[CH3:1][C@H:2]([NH:3][c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([O:11][CH2:12][CH2:13]...
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccc(-c2cnc3ncnn3c2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
67.7
[{"value": 67.7, "product": "ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCN(C)C)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
null
null
To a solution of 5-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine (600 mg, 1.5 mmol) and 3-dimethylamino-1-propanol (1.03 g, 10 mmol) in 5 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 400 mg, 10 mmol). The mixtur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1cnc2ncnn2c1
HF
CS(=O)C
50
null
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F>CS(=O)C>C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-15120b4bcb65405e8de97b2df43db45d
CNCCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F>>CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2N[C@@H](C)C(F)(F)F)c(F)c1
[H-].[Na+].CNCCCO.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2>>ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2
[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][OH:6].F[c:7]1[cH:8][c:9]([F:10])[c:11](-[c:12]2[c:13]([Cl:14])[n:15][c:16]3[n:17][cH:18][n:19][n:20]3[c:21]2[NH:22][C@@H:23]([CH3:24])[C:25]([F:26])([F:27])[F:28])[c:29]([F:30])[cH:31]1>>[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][O:6][c:7]1[cH:8][c:9]([F:10])[c:11](-[c:12]2[c:13]([Cl:14])[n:1...
CNCCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F
CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2N[C@@H](C)C(F)(F)F)c(F)c1
null
null
CS(=O)C.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccc(-c2cnc3ncnn3c2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
40.3
[{"value": 40.3, "product": "ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To sodium hydride (60% in mineral oil, 2.3 g, 57.6 mmol) in 20 mL of dimethylsulfoxide at room temperature is added a solution of 3-(methylamino)propan-1-ol (5.14 g, 57.6 mmol) in 10 mL of dimethylsulfoxide. The solution is stirred at room temperature for 1 h, and 5-chloro-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-triflu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1cnc2ncnn2c1
HF
CS(=O)C.C(C)(=O)OCC
null
1
CNCCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Cl)nc2ncnn12)C(F)(F)F>CS(=O)C.C(C)(=O)OCC>CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2N[C@@H](C)C(F)(F)F)c(F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b9c8180031aa41cca7822ea0b32bd159
O=C(O)/C=C/C(=O)O>>O=C(O)/C=C/C(=O)O
C(\C=C\C(=O)O)(=O)O.Cl.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2.[OH-].[Na+]>>C(\C=C\C(=O)O)(=O)O.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2
[O:32]=[C:33]([OH:34])/[CH:35]=[CH:36]/[C:37](=[O:38])[OH:39]>>[O:32]=[C:33]([OH:34])/[CH:35]=[CH:36]/[C:37](=[O:38])[OH:39]
O=C(O)/C=C/C(=O)O
O=C(O)/C=C/C(=O)O
null
null
O
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
75.1
[{"value": 75.0, "product": "C(\\C=C\\C(=O)O)(=O)O.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.1, "product": "C(\\C=C\\C(=O)O)(=O)O.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "...
70
CELSIUS
17.5
MINUTE
To a slurry of 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine hydrochloride (7.50 g, 15.0 mmol) and water (100 mL) is added sodium hydroxide solution (10 N, 2.0 mL, 20 mmol) dropwise. Then, fumaric acid (3.48 g, 30 mmol) is added....
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
O
70
0.291667
O=C(O)/C=C/C(=O)O>O>O=C(O)/C=C/C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-999b25e3cb2d4cecb12b24dfd9489389
O=C(O)CCC(=O)O>>O=C(O)CCC(=O)O
ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2.C(CCC(=O)O)(=O)O>>C(CCC(=O)O)(=O)O.ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCNC)F)N[C@H](C(F)(F)F)C)N=CN2
[O:32]=[C:33]([OH:34])[CH2:35][CH2:36][C:37](=[O:38])[OH:39]>>[O:32]=[C:33]([OH:34])[CH2:35][CH2:36][C:37](=[O:38])[OH:39]
O=C(O)CCC(=O)O
O=C(O)CCC(=O)O
null
null
O
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
70
CELSIUS
17.5
MINUTE
A mixture of 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine (9.00 g, 19.4 mmol) and succinic acid (2.75 g, 23.3 mmol) in water (90 mL) is stirred for about 15-20 min and then heated to about 65-75° C. The solution is filtered and ...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
O
70
0.291667
O=C(O)CCC(=O)O>O>O=C(O)CCC(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c47997c64243437f9f2f3d828ae764c4
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Br)nc3ncnn3c2Br)c(F)c1>>C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F
O.BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)Br)N=CN2.Cl.FC([C@H](C)N)(F)F.C(C)(C)N(CC)C(C)C>>BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2
[CH3:1][C@H:2]([NH2:3])[C:23]([F:24])([F:25])[F:26].Br[c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([F:11])[cH:12][c:13]2[F:14])[c:15]([Br:16])[n:17][c:18]2[n:19][cH:20][n:21][n:22]12>>[CH3:1][C@H:2]([NH:3][c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([F:11])[cH:12][c:13]2[F:14])[c:15]([Br:16])[n:17][c:18]2[n:19][cH:20][n:...
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Br)nc3ncnn3c2Br)c(F)c1
C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
680ce65987443e27ed1de90a7e61da2b858a904becdcfebe764b8f0fdb130b5c
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2cnc3ncnn3c2)cc1
Br-[c;H0;D3;+0:1]1:[#7;a:2]2:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]:2:[#7;a:7]:[c:8](-[Br;D1;H0:9]):[c:10]:1-[c:11].[C;D1;H3:12]-[C:13](-[NH2;D1;+0:14])-[C:15](-[F;D1;H0:16])(-[F;D1;H0:17])-[F;D1;H0:18]>>[Br;D1;H0:9]-[c:8]1:[#7;a:7]:[c:6]2:[#7;a:5]:[c:4]:[#7;a:3]:[#7;a:2]:2:[c;H0;D3;+0:1](-[NH;D2;+0:14]-[C:13](-[C;D1;H3:12])-[C...
17.5
[{"value": 17.5, "product": "BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A mixture of 5,7-dibromo-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine (320 mg, 0.78 mmol), (1S)-2,2,2-trifluoro-1-methylethylamine hydrogen chloride (235 mg, 1.57 mmol), and diisopropylethylamine (260 mg, 2.0 mmol) in 5 mL of N,N-dimethylformamide is stirred at room temperature for 18 h. Water is added to ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2ncnn2c1
c1cnc2ncnn2c1
c1ccccc1.c1cnc2ncnn2c1
HBr
CN(C=O)C
null
18
C[C@H](N)C(F)(F)F.Fc1cc(F)c(-c2c(Br)nc3ncnn3c2Br)c(F)c1>CN(C=O)C>C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-598882ca8c114ffba921317d4c245de0
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F>>C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Br)nc2ncnn12)C(F)(F)F
O.BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)F)F)N[C@H](C(F)(F)F)C)N=CN2.CN(CCCO)C.[H-].[Na+]>>BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCN(C)C)F)N[C@H](C(F)(F)F)C)N=CN2
[OH:11][CH2:12][CH2:13][CH2:14][N:15]([CH3:16])[CH3:17].F[c:10]1[cH:9][c:7]([F:8])[c:6](-[c:5]2[c:4]([NH:3][C@@H:2]([CH3:1])[C:29]([F:30])([F:31])[F:32])[n:28]3[c:24]([n:23][c:21]2[Br:22])[n:25][cH:26][n:27]3)[c:19]([F:20])[cH:18]1>>[CH3:1][C@H:2]([NH:3][c:4]1[c:5](-[c:6]2[c:7]([F:8])[cH:9][c:10]([O:11][CH2:12][CH2:13]...
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F
C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Br)nc2ncnn12)C(F)(F)F
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccc(-c2cnc3ncnn3c2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
78.3
[{"value": 78.3, "product": "BrC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCN(C)C)F)N[C@H](C(F)(F)F)C)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
To a solution of 5-bromo-6-(2,4,6-trifluorophenyl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine (44 mg, 0.1 mmol) and 3-dimethylamino-1-propanol (51 m g, 0.5 mmol) in 1 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 20 mg, 0.5 mmol). The mixture...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1cnc2ncnn2c1
HF
CS(=O)C
60
null
CN(C)CCCO.C[C@H](Nc1c(-c2c(F)cc(F)cc2F)c(Br)nc2ncnn12)C(F)(F)F>CS(=O)C>C[C@H](Nc1c(-c2c(F)cc(OCCCN(C)C)cc2F)c(Br)nc2ncnn12)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-46c8f9dfedd640ea8424108be2403a20
CCOC(=O)C(C(=O)OCC)c1c(F)cc(OC)cc1F>>CCOC(=O)C(C(=O)OCC)c1c(F)cc(O)cc1F
C([O-])(O)=O.[Na+].FC1=C(C(=CC(=C1)OC)F)C(C(=O)OCC)C(=O)OCC.B(Br)(Br)Br>>FC1=C(C(=CC(=C1)O)F)C(C(=O)OCC)C(=O)OCC
C[O:17][c:16]1[cH:15][c:13]([F:14])[c:12]([CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[C:7](=[O:8])[O:9][CH2:10][CH3:11])[c:19]([F:20])[cH:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([C:7](=[O:8])[O:9][CH2:10][CH3:11])[c:12]1[c:13]([F:14])[cH:15][c:16]([OH:17])[cH:18][c:19]1[F:20]
CCOC(=O)C(C(=O)OCC)c1c(F)cc(OC)cc1F
CCOC(=O)C(C(=O)OCC)c1c(F)cc(O)cc1F
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccccc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
94.7
[{"value": 94.7, "product": "FC1=C(C(=CC(=C1)O)F)C(C(=O)OCC)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-78
CELSIUS
10
MINUTE
To a solution of diethyl 2-(2,6-difluoro-4-methoxyphenyl)malonate (2.11 g, 7.0 mmol) in 60 mL of methylene chloride at −78° C. is added boron tribromide (2.65 mL, 28 mmol) dropwise. The mixture is then stirred at −78° C. for 10 minutes, warmed to 0° C., and stirred at 0° C. for 1 h. A 5% aqueous solution of sodium bica...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1
Other
C(Cl)Cl
-78
0.166667
CCOC(=O)C(C(=O)OCC)c1c(F)cc(OC)cc1F>C(Cl)Cl>CCOC(=O)C(C(=O)OCC)c1c(F)cc(O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9d939f4404c241e5b2b77e09326f51eb
C=CCCO.CCOC(=O)C(C(=O)OCC)c1c(F)cc(OS(=O)(=O)C(F)(F)F)cc1F>>CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCO)cc1F
C[N+](C)(C)[O-].FC1=C(C(=CC(=C1)OS(=O)(=O)C(F)(F)F)F)C(C(=O)OCC)C(=O)OCC.P(=O)([O-])([O-])[O-].[K+].[K+].[K+].C12CCCC(CCC1)B2.O1CCCC1.C(CC=C)O>>FC1=C(C(=CC(=C1)CCCCO)F)C(C(=O)OCC)C(=O)OCC
[CH2:17]=[CH:18][CH2:19][CH2:20][OH:21].O=S(=O)(O[c:16]1[cH:15][c:13]([F:14])[c:12]([CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[C:7](=[O:8])[O:9][CH2:10][CH3:11])[c:23]([F:24])[cH:22]1)C(F)(F)F>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([C:7](=[O:8])[O:9][CH2:10][CH3:11])[c:12]1[c:13]([F:14])[cH:15][c:16]([CH2:17][CH2:18][CH...
C=CCCO.CCOC(=O)C(C(=O)OCC)c1c(F)cc(OS(=O)(=O)C(F)(F)F)cc1F
CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCO)cc1F
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1.C(C)(=O)OCC
C-C Coupling
OtherReaction
984b78f4f8d59098e10d908843a5bc85917f55238c2f2137d4efc412864d5e7c
dc8d671a2733f8ed24a0522b611e130eb3e91983213ee2751322bb6d51e1830f
c1ccccc1
F-C(-F)(-F)-S(=O)(=O)-O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[CH;D2;+0:8]=[CH2;D1;+0:9]>>[C:6]-[C:7]-[CH2;D2;+0:8]-[CH2;D2;+0:9]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
42.7
[{"value": 42.7, "product": "FC1=C(C(=CC(=C1)CCCCO)F)C(C(=O)OCC)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
To a 0.5 M solution of 9-borabicyclo[3.3.1]nonane (9-BBN) in tetrahydrofuran (95 mL, 47.6 mmol) is added dropwise 3-butene-1-ol (4.1 mL, 47.6 mmol), and the mixture is stirred under nitrogen atmosphere at room temperature for 6 h. The resulting solution is then transferred by a double-ended needle into a mixture of die...
10.6084/m9.figshare.5104873.v1
null
Triflate.Allyl
null
c1ccccc1
c1ccccc1
c1ccccc1
TfOH
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1.C(C)(=O)OCC
null
6
C=CCCO.CCOC(=O)C(C(=O)OCC)c1c(F)cc(OS(=O)(=O)C(F)(F)F)cc1F>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1.C(C)(=O)OCC>CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCO)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d092c670c40a423091b1f4ce5020007d
CCN(CC)CC.CCNCC.O=C([O-])C(C(=O)[O-])c1c(F)cc(CCCCO)cc1F>>CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F
C(C)NCC.O1CCCC1.FC1=C(C(=CC(=C1)CCCCO)F)C(C(=O)[O-])C(=O)[O-].C(C)N(CC)CC.CS(=O)(=O)Cl>>CN(CCCCC1=CC(=C(C(=C1)F)C(C(=O)OCC)C(=O)OCC)F)C
CCN(CC)[CH2:2][CH3:1].[CH2:10]([CH3:11])[NH:21][CH2:22][CH3:23].O[CH2:20][CH2:19][CH2:18][CH2:17][c:16]1[cH:15][c:13]([F:14])[c:12]([CH:6]([C:4]([O-:3])=[O:5])[C:7](=[O:8])[O-:9])[c:25]([F:26])[cH:24]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([C:7](=[O:8])[O:9][CH2:10][CH3:11])[c:12]1[c:13]([F:14])[cH:15][c:16]([CH2:17]...
CCN(CC)CC.CCNCC.O=C([O-])C(C(=O)[O-])c1c(F)cc(CCCCO)cc1F
CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
ea1d3c1d4a39334b9eb50b36f005cb6aa33430995fc3f0d75d155838aa416985
f35b1eede046205811cbd9c28631f641d27eb5341a50b573f6e75427ea64ca20
c1ccccc1
C-C-N(-C-C)-[CH2;D2;+0:1]-[C;D1;H3:2].O-[CH2;D2;+0:3]-[C:4]-[C:5].[O-;H0;D1:6]-[C:7](=[O;D1;H0:8])-[C:9]-[C:10](-[O-;H0;D1:11])=[O;D1;H0:12].[C;D1;H3:13]-[CH2;D2;+0:14]-[NH;D2;+0:15]-[CH2;D2;+0:16]-[CH3;D1;+0:17]>>[C;D1;H3:13]-[CH2;D2;+0:14]-[O;H0;D2;+0:11]-[C:10](=[O;D1;H0:12])-[C:9]-[C:7](=[O;D1;H0:8])-[O;H0;D2;+0:6]...
null
[]
null
null
null
null
To a solution of 2-[2,6-difluoro-4-(4-hydroxybutyl)phenyl]malonate (2.0 g, 5.8 mmol) and triethylamine (2.43 mL, 17.4 mmol) in 15 ml of methylene chloride at 0° C. is added methanesulfonyl chloride (0.898 mL, 11.6 mmol). The resulting mixture is allowed to warm to room temperature in 1.5 h. The mixture is washed with 1...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Secondary amine.Tertiary amine
Ester.Ester.Tertiary amine
null
null
c1ccccc1
HO-
C(Cl)Cl
null
null
CCN(CC)CC.CCNCC.O=C([O-])C(C(=O)[O-])c1c(F)cc(CCCCO)cc1F>C(Cl)Cl>CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2a61d1b6715b43a299f9e27b945d04ce
CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F.Nc1nc[nH]n1>>CN(C)CCCCc1cc(F)c(-c2c(O)nc3ncnn3c2O)c(F)c1
CN(CCCCC1=CC(=C(C(=C1)F)C(C(=O)OCC)C(=O)OCC)F)C.NC1=NNC=N1.C(CCC)N(CCCC)CCCC>>CN(CCCCC1=CC(=C(C(=C1)F)C=1C(=NC=2N(C1O)N=CN2)O)F)C
CCO[C:14]([CH:13]([c:12]1[c:10]([F:11])[cH:9][c:8]([CH2:7][CH2:6][CH2:5][CH2:4][N:2]([CH3:1])[CH3:3])[cH:26][c:24]1[F:25])[C:22](OCC)=[O:23])=[O:15].[NH2:16][c:17]1[n:18][cH:19][nH:20][n:21]1>>[CH3:1][N:2]([CH3:3])[CH2:4][CH2:5][CH2:6][CH2:7][c:8]1[cH:9][c:10]([F:11])[c:12](-[c:13]2[c:14]([OH:15])[n:16][c:17]3[n:18][cH...
CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F.Nc1nc[nH]n1
CN(C)CCCCc1cc(F)c(-c2c(O)nc3ncnn3c2O)c(F)c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
ac7d5d1285ecbc0fc0c7df5cb8115ebe0ad026b9f23bb1406929cb0426c46965
6504f33921726f64e36c5f3f322459b73652319c83071522ec21b8b88a33a5a7
c1ccc(-c2cnc3ncnn3c2)cc1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH;D3;+0:3](-[C;H0;D3;+0:4](=[O;H0;D1;+0:5])-O-C-C)-[c;H0;D3;+0:6](:[c:7](-[F;D1;H0:8]):[c:9]):[c:10](-[F;D1;H0:11]):[c:12].[NH2;D1;+0:13]-[c:14]1:[#7;a:15]:[c:16]:[nH;D2;+0:17]:[n;H0;D2;+0:18]:1>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:6](-[c;H0;D3;+0:3]1:[c;H0;D3;+0:1](-[OH;D1;+0:...
81
[{"value": 81.0, "product": "CN(CCCCC1=CC(=C(C(=C1)F)C=1C(=NC=2N(C1O)N=CN2)O)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
160
CELSIUS
16
HOUR
A mixture of diethyl 2-{4-[4-(dimethylamino)butyl]-2,6-difluorophenyl]malonate (1.0 g, 2.7 mmol), 3-amino-1,2,4-triazole (250 mg, 3.0 mmol), and tributylamine (0.71 mL, 3.0 mmol) is stirred under nitrogen atmosphere at 160° C. for 16 h and cooled to room temperature. The mixture is stirred with 20 ml of hexanes. The pr...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Primary amine
Aromatic alcohol.Aromatic alcohol
c1nnc[nH]1
c1cnc2ncnn2c1
c1ccccc1.c1cnc2ncnn2c1
HO-
null
160
16
CCOC(=O)C(C(=O)OCC)c1c(F)cc(CCCCN(C)C)cc1F.Nc1nc[nH]n1>>CN(C)CCCCc1cc(F)c(-c2c(O)nc3ncnn3c2O)c(F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-013a65e7184744e295e31a6ef981ae6d
CCI.O=C(O)Cc1c(F)cc(F)cc1F>>CCOC(=O)Cc1c(F)cc(F)cc1F
FC1=C(C(=CC(=C1)F)F)CC(=O)O.ICC.C([O-])([O-])=O.[K+].[K+]>>FC1=C(C(=CC(=C1)F)F)CC(=O)OCC
I[CH2:2][CH3:1].[OH:3][C:4](=[O:5])[CH2:6][c:7]1[c:8]([F:9])[cH:10][c:11]([F:12])[cH:13][c:14]1[F:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:7]1[c:8]([F:9])[cH:10][c:11]([F:12])[cH:13][c:14]1[F:15]
CCI.O=C(O)Cc1c(F)cc(F)cc1F
CCOC(=O)Cc1c(F)cc(F)cc1F
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
06c4f868ad4646eea8208ecb83f54ca035dd62d04f0d8101641a4f487f2c695c
8446834f0edd1e71a2dcaffc09b80c7367abf3407263a8998354a2d20c1766bb
c1ccccc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[C:3]-[C:4](=[O;D1;H0:5])-[OH;D1;+0:6]>>[C:3]-[C:4](=[O;D1;H0:5])-[O;H0;D2;+0:6]-[CH2;D2;+0:1]-[C;D1;H3:2]
88.7
[{"value": 88.7, "product": "FC1=C(C(=CC(=C1)F)F)CC(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
3
HOUR
A mixture of 2,4,6-trifluorophenylacetic acid (570 mg, 3.0 mmol), iodoethane (1.56 g, 10 mmol), and potassium carbonate (1.38 g, 10 mmol) in 5 mL of dimethylsulfoxide is stirred at 50° C. for 3 h, and cooled to room temperature. The mixture is partitioned between diethyl ether and water. The organic layer is washed wit...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carboxylic acid
Ester
null
null
c1ccccc1
HI
CS(=O)C
50
3
CCI.O=C(O)Cc1c(F)cc(F)cc1F>CS(=O)C>CCOC(=O)Cc1c(F)cc(F)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-782ec82f14a14050bce378ccea8104f8
CCOC(=O)Cc1c(F)cc(F)cc1F.O=C(Cl)C1CCCCCC1>>CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F
Cl.C(C)(C)[N-]C(C)C.[Li+].FC1=C(C(=CC(=C1)F)F)CC(=O)OCC.C1(CCCCCC1)C(=O)Cl>>C1(CCCCCC1)C(C(C(=O)OCC)C1=C(C=C(C=C1F)F)F)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:16]1[c:17]([F:18])[cH:19][c:20]([F:21])[cH:22][c:23]1[F:24].Cl[C:7](=[O:8])[CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([C:7](=[O:8])[CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1)[c:16]1[c:17]([F:18])[cH:19][c:20]([...
CCOC(=O)Cc1c(F)cc(F)cc1F.O=C(Cl)C1CCCCCC1
CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F
null
null
O1CCCC1
C-C Coupling
OtherReaction
9c255438d8e6adeba9ee52582b8e97af5f85bef382cd416953270ac55bd10486
4c7bc8856483317e0c04a17d8cd6aba13cdf5ed9f64b61fe01f230a819039f82
O=C(Cc1ccccc1)C1CCCCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[C:6]-[#8:7]-[C:8](=[O;D1;H0:9])-[CH2;D2;+0:10]-[c:11](:[c:12]):[c:13]>>[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH;D3;+0:10](-[C:8](=[O;D1;H0:9])-[#8:7]-[C:6])-[c:11](:[c:12]):[c:13])-[C:5]
59.9
[{"value": 59.9, "product": "C1(CCCCCC1)C(C(C(=O)OCC)C1=C(C=C(C=C1F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of ethyl 2,4,6-trifluorophenylacetate (436 mg, 2.0 mmol) in 3 mL of tetrahydrofuran is cooled to −78° C., and lithium diisopropylamide (2.0 M in heptane/tetrahydrofuran/ethylbenzene, 1.0 mL, 2.0 mmol) is added dropwise with stirring. The mixture is stirred at −78° C. for 1 h, and cycloheptanecarboxylic acid ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ester
Ketone
null
null
C1CCCCCC1.c1ccccc1
HCl
O1CCCC1
null
null
CCOC(=O)Cc1c(F)cc(F)cc1F.O=C(Cl)C1CCCCCC1>O1CCCC1>CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5bec2205b16f45e0a6de23685051a431
CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F.Nc1nc[nH]n1>>Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
C1(CCCCCC1)C(C(C(=O)OCC)C1=C(C=C(C=C1F)F)F)=O.NC1=NNC=N1.C(CCC)N(CCCC)CCCC>>C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)F)F
CCO[C:2](=[O:1])[CH:17]([C:9](=O)[CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1)[c:18]1[c:19]([F:20])[cH:21][c:22]([F:23])[cH:24][c:25]1[F:26].[NH2:3][c:4]1[n:5][cH:6][nH:7][n:8]1>>[OH:1][c:2]1[n:3][c:4]2[n:5][cH:6][n:7][n:8]2[c:9]([CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)[c:17]1-[c:18]1[c:1...
CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F.Nc1nc[nH]n1
Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
null
null
C(C)(=O)OCC
Aromatic Heterocycle Formation
OtherReaction
7674ff7d462a618e5b3752017402cc7a7f8449f1e25dd52bd8b91ea1a45dc06e
e4cbab44abd9117eb42f959793b157d31b1dce9de3f9c3954c67bf975e572e43
c1ccc(-c2cnc3ncnn3c2C2CCCCCC2)cc1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH;D3;+0:3](-[C;H0;D3;+0:4](=O)-[C:5](-[C:6])-[C:7])-[c;H0;D3;+0:8](:[c:9](-[F;D1;H0:10]):[c:11]):[c:12](-[F;D1;H0:13]):[c:14].[NH2;D1;+0:15]-[c:16]1:[#7;a:17]:[c:18]:[nH;D2;+0:19]:[n;H0;D2;+0:20]:1>>[C:6]-[C:5](-[c;H0;D3;+0:4]1:[c;H0;D3;+0:3](-[c;H0;D3;+0:8](:[c:9](-[F;D1;H0:10])...
62.1
[{"value": 62.1, "product": "C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
160
CELSIUS
2.5
HOUR
A mixture of ethyl 3-cycloheptyl-3-oxo-2-(2,4,6-trifluorophenyl)propanoate (342 mg, 1.0 mmol), 3-amino-1,2,4-triazole (84 mg, 1.0 mmol), and tributylamine (185 mg, 1.0 mmol) is stirred under nitrogen atmosphere at 160° C. for 2.5 h and cooled to room temperature. The mixture is dissolved in ethyl acetate and the organi...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Primary amine
Aromatic alcohol
c1nnc[nH]1
c1cnc2ncnn2c1
c1cnc2ncnn2c1.C1CCCCCC1.c1ccccc1
HO-
C(C)(=O)OCC
160
2.5
CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F.Nc1nc[nH]n1>C(C)(=O)OCC>Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-12ea2415dfc34ab38ffedece9c45e59f
COc1ccc(COCCCO)cc1.Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F>>COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)F)F.COC1=CC=C(COCCCO)C=C1.[H-].[Na+]>>C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)OCCCOCC2=CC=C(C=C2)OC)F
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][O:8][CH2:9][CH2:10][CH2:11][OH:12])[cH:38][cH:39]1.F[c:13]1[cH:14][c:15]([F:16])[c:17](-[c:18]2[c:19]([OH:20])[n:21][c:22]3[n:23][cH:24][n:25][n:26]3[c:27]2[CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)[c:35]([F:36])[cH:37]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C...
COc1ccc(COCCCO)cc1.Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccc(COCCCOc2ccc(-c3cnc4ncnn4c3C3CCCCCC3)cc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
152.3
[{"value": 152.3, "product": "C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)OCCCOCC2=CC=C(C=C2)OC)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 7-cycloheptyl-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-5-ol (362 mg, 1.0 mmol) and 3-[(4-methoxybenzyl)oxy]-1-propanol (490 mg, 2.5 mmol) in 4.0 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 120 mg, 3.0 mmol). The mixture is stirred at room tem...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1cnc2ncnn2c1.C1CCCCCC1
HF
CS(=O)C
null
3
COc1ccc(COCCCO)cc1.Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F>CS(=O)C>COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c65bec13f6af40bfa291e2b9ee177f76
COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1.O=P(Cl)(Cl)Cl>>COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(C=C2F)OCCCOCC2=CC=C(C=C2)OC)F.P(=O)(Cl)(Cl)Cl.C(C)N(C1=CC=CC=C1)CC>>ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCOCC1=CC=C(C=C1)OC)F)C1CCCCCC1)N=CN2
O[c:19]1[c:18](-[c:17]2[c:15]([F:16])[cH:14][c:13]([O:12][CH2:11][CH2:10][CH2:9][O:8][CH2:7][c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:39][cH:38]3)[cH:37][c:35]2[F:36])[c:27]([CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)[n:26]2[c:22]([n:21]1)[n:23][cH:24][n:25]2.O=P(Cl)(Cl)[Cl:20]>>[CH3:1][O:2][c:3]1[cH:4][c...
COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1.O=P(Cl)(Cl)Cl
COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_ortho
0931592c624e33b002d2d3727976d0e1d5e44a0d838cefe4b8b67627403baf59
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(COCCCOc2ccc(-c3cnc4ncnn4c3C3CCCCCC3)cc2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]2:[#7;a:5]:[c:6]:[#7;a:7]:[#7;a:8]:2:[c:9](-[C:10]):[c:11]:1-[c:12]>>[C:10]-[c:9]1:[#7;a:8]2:[#7;a:7]:[c:6]:[#7;a:5]:[c:4]:2:[#7;a:3]:[c;H0;D3;+0:2](-[Cl;H0;D1;+0:1]):[c:11]:1-[c:12]
null
[]
null
null
null
null
To the above 7-cycloheptyl-6-(2,6-difluoro-4-{3-[(4-methoxybenzyl)oxy]propoxy}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-5-ol (820 mg) is added 5 mL of phosphorous oxychloride and 2 mL of N,N-diethylaniline, and the mixture is heated at reflux for 1 h. The excess phosphorous oxychloride is removed in vaccuo, and the result...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1cnc2ncnn2c1
c1cnc2ncnn2c1
c1ccccc1.c1ccccc1.c1cnc2ncnn2c1.C1CCCCCC1
HCl
null
null
null
COc1ccc(COCCCOc2cc(F)c(-c3c(O)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1.O=P(Cl)(Cl)Cl>>COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3649847cac1f4e6e99f14d8a98d7a75d
COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1>>OCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
ClC1=NC=2N(C(=C1C1=C(C=C(C=C1F)OCCCOCC1=CC=C(C=C1)OC)F)C1CCCCCC1)N=CN2.ClC=1C(C(=C(C(C1Cl)=O)C#N)C#N)=O>>ClC1=NC=2N(C(=C1C1=C(C=C(OCCCO)C=C1F)F)C1CCCCCC1)N=CN2
COc1ccc(C[O:1][CH2:2][CH2:3][CH2:4][O:5][c:6]2[cH:7][c:8]([F:9])[c:10](-[c:11]3[c:12]([Cl:13])[n:14][c:15]4[n:16][cH:17][n:18][n:19]4[c:20]3[CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]3)[c:28]([F:29])[cH:30]2)cc1>>[OH:1][CH2:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][c:8]([F:9])[c:10](-[c:11]2[c:12]([Cl:13])[n:14][c...
COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1
OCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
null
null
O.C(Cl)Cl
Reduction
Cleavage of alkoxy ethers to alcohols
b9cb0e2e22c551f08401a6ebf7cca400a853b5888643e64a72f0d14fdf16154a
a4561cbdd42f56679299e19ea8b11070a39a15f6a95fb8a877e677f11b7ff57f
c1ccc(-c2cnc3ncnn3c2C2CCCCCC2)cc1
C-O-c1:c:c:c(-C-[O;H0;D2;+0:1]-[C:2]-[C:3]):c:c:1>>[C:3]-[C:2]-[OH;D1;+0:1]
77.8
[{"value": 77.8, "product": "ClC1=NC=2N(C(=C1C1=C(C=C(OCCCO)C=C1F)F)C1CCCCCC1)N=CN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
To a solution of 5-chloro-7-cycloheptyl-6-(2,6-difluoro-4-{3-[(4-methoxybenzyl)oxy]propoxy}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine (56 mg, 0.1 mmol) in 4 mL of methylene chloride and 0.2 mL of water is added 2,3-dichloro-5,6-dicyano-1,4-bezoquinone (100 mg, 0.44 mmol). The mixture is stirred at room temperature for 20 ...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol
c1ccccc1
null
c1ccccc1.c1cnc2ncnn2c1.C1CCCCCC1
HO-
O.C(Cl)Cl
null
0.333333
COc1ccc(COCCCOc2cc(F)c(-c3c(Cl)nc4ncnn4c3C3CCCCCC3)c(F)c2)cc1>O.C(Cl)Cl>OCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ba1810bfcb95419989b90d1ac1d93088
CN(CCCOc1cc(F)c(-c2c(O)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C.O=P(Cl)(Cl)Cl>>CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C
C1(CCCCCC1)C1=C(C(=NC=2N1N=CN2)O)C2=C(C=C(OCCCN(C(OC(C)(C)C)=O)C)C=C2F)F.P(=O)(Cl)(Cl)Cl.C(C)N(C1=CC=CC=C1)CC>>ClC1=NC=2N(C(=C1C1=C(C=C(OCCCN(C(OC(C)(C)C)=O)C)C=C1F)F)C1CCCCCC1)N=CN2
O[c:13]1[c:12](-[c:11]2[c:9]([F:10])[cH:8][c:7]([O:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[C:32](=[O:33])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])[cH:31][c:29]2[F:30])[c:21]([CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)[n:20]2[c:16]([n:15]1)[n:17][cH:18][n:19]2.O=P(Cl)(Cl)[Cl:14]>>[CH3:1][N:2]([CH2:3][CH2:4]...
CN(CCCOc1cc(F)c(-c2c(O)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C.O=P(Cl)(Cl)Cl
CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_ortho
0931592c624e33b002d2d3727976d0e1d5e44a0d838cefe4b8b67627403baf59
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(-c2cnc3ncnn3c2C2CCCCCC2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]2:[#7;a:5]:[c:6]:[#7;a:7]:[#7;a:8]:2:[c:9](-[C:10]):[c:11]:1-[c:12]>>[C:10]-[c:9]1:[#7;a:8]2:[#7;a:7]:[c:6]:[#7;a:5]:[c:4]:2:[#7;a:3]:[c;H0;D3;+0:2](-[Cl;H0;D1;+0:1]):[c:11]:1-[c:12]
null
[]
90
CELSIUS
null
null
To tert-butyl 3-[4-(7-cycloheptyl-5-hydroxy[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-3,5-difluorophenoxy]propyl(methyl)carbamate (876 mg, 1.64 mmol) is added 5.8 mL of phosphorous oxychloride and 2.9 mL of N,N-diethylaniline, and the mixture is heated at 90° C. for 3 h. The excess phosphorous oxychloride is removed in vacc...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1cnc2ncnn2c1
c1cnc2ncnn2c1
c1ccccc1.c1cnc2ncnn2c1.C1CCCCCC1
HCl
null
90
null
CN(CCCOc1cc(F)c(-c2c(O)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C.O=P(Cl)(Cl)Cl>>CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-94fdb62393a8470388014bda6354dcec
CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C>>CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
ClC1=NC=2N(C(=C1C1=C(C=C(OCCCN(C(OC(C)(C)C)=O)C)C=C1F)F)C1CCCCCC1)N=CN2.FC(C(=O)O)(F)F>>ClC1=NC=2N(C(=C1C1=C(C=C(OCCCNC)C=C1F)F)C1CCCCCC1)N=CN2.FC(C(=O)O)(F)F
CC(C)(C)OC(=O)[N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][c:7]1[cH:8][c:9]([F:10])[c:11](-[c:12]2[c:13]([Cl:14])[n:15][c:16]3[n:17][cH:18][n:19][n:20]3[c:21]2[CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)[c:29]([F:30])[cH:31]1>>[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][O:6][c:7]1[cH:8][c:9]([F:10])[c:11](-[c:12]2[c:1...
CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C
CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(-c2cnc3ncnn3c2C2CCCCCC2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C;D1;H3:2])-[C:3]-[C:4]>>[C:4]-[C:3]-[NH;D2;+0:1]-[C;D1;H3:2]
null
[]
null
null
18
HOUR
To a solution of tert-butyl 3-[4-(5-chloro-7-cycloheptyl [1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-3,5-difluorophenoxy]propyl(methyl)carbamate (452 mg, 0.82 mmol) in 4 mL of methylene chloride is added 2.3 mL of trifluoroacetic acid. The mixture is stirred at room temperature for 18 h, and concentrated in vaccuo, yielding ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccccc1.c1cnc2ncnn2c1.C1CCCCCC1
HO-
C(Cl)Cl
null
18
CN(CCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1)C(=O)OC(C)(C)C>C(Cl)Cl>CNCCCOc1cc(F)c(-c2c(Cl)nc3ncnn3c2C2CCCCCC2)c(F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e3f93ad66dc84c42b016b81a12837149
O=C(O)c1cc(Br)cnc1O.O=S(Cl)Cl>>O=C(O)c1cccnc1Cl
BrC=1C=NC(=C(C(=O)O)C1)O.S(=O)(Cl)Cl>>ClC1=C(C(=O)O)C=CC=N1
O[c:9]1[c:4]([C:2](=[O:1])[OH:3])[cH:5][c:6](Br)[cH:7][n:8]1.O=S(Cl)[Cl:10]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][cH:7][n:8][c:9]1[Cl:10]
O=C(O)c1cc(Br)cnc1O.O=S(Cl)Cl
O=C(O)c1cccnc1Cl
null
null
null
Functional Group Interconversion
OtherReaction
b61615ffa3205a9db4043261b57050bc62cd6c2df82599ac04be5637ae28995c
c82cc461af6e06935dddeb6b9f92147f67674f1d402fa9a7706939b230a523c5
c1ccncc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[C:4](=[O;D1;H0:5])-[O;D1;H1:6]):[c;H0;D3;+0:7](-O):[#7;a:8]:[c:9]:1.Cl-S(=O)-[Cl;H0;D1;+0:10]>>[Cl;H0;D1;+0:10]-[c;H0;D3;+0:7]1:[#7;a:8]:[c:9]:[cH;D2;+0:1]:[c:2]:[c:3]:1-[C:4](=[O;D1;H0:5])-[O;D1;H1:6]
null
[]
null
null
null
null
Substituted pyridines 12 can be prepared by the procedure described in Scheme 4. A solution of sodium hypobromite is freshly prepared and added to a 2-hydroxynicotinic acid 7 and heated, such as at a temperature of about 50° C. Additional sodium hypobromide may be added to form the bromo compound 8 as needed. The 5-bro...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
Br-
null
null
null
O=C(O)c1cc(Br)cnc1O.O=S(Cl)Cl>>O=C(O)c1cccnc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2c94a1ace22b40abb15775032c237108
O=[N+]([O-])c1ccc2c(Oc3n[nH]c4cc([N+](=O)[O-])ccc34)n[nH]c2c1>>Nc1ccc2c(Oc3n[nH]c4cc(N)ccc34)n[nH]c2c1
[N+](=O)([O-])C1=CC=C2C(=NNC2=C1)OC1=NNC2=CC(=CC=C12)[N+](=O)[O-]>>NC1=CC=C2C(=NNC2=C1)OC1=NNC2=CC(=CC=C12)N
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]2[c:6]([O:7][c:8]3[n:9][nH:10][c:11]4[cH:12][c:13]([N+:14](=O)[O-])[cH:15][cH:16][c:17]34)[n:18][nH:19][c:20]2[cH:21]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([O:7][c:8]3[n:9][nH:10][c:11]4[cH:12][c:13]([NH2:14])[cH:15][cH:16][c:17]34)[n:18][nH:19][c:20]2[cH:21]1
O=[N+]([O-])c1ccc2c(Oc3n[nH]c4cc([N+](=O)[O-])ccc34)n[nH]c2c1
Nc1ccc2c(Oc3n[nH]c4cc(N)ccc34)n[nH]c2c1
null
[Pd]
null
Reduction
OtherReaction
6748a51a25102225412593c5a930e43f5a8904a80803177de025a6f83c59d65e
a303b0dfb15cc6bade463acf71681cf3ba7580b599dfa4d28d8caac83d08cd17
c1ccc2c(Oc3n[nH]c4ccccc34)n[nH]c2c1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6].O=[N+;H0;D3:7](-[O-])-[c:8](:[c:9]):[c:10]:[c:11]:[#7;a:12]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3].[#7;a:12]:[c:11]:[c:10]:[c:8](-[NH2;D1;+0:7]):[c:9]
null
[]
null
null
null
null
Indazolyl ethers 38 can be prepared by the procedure described in Scheme 13. 6-Nitro-1H-2-hydroindazol-3-one 37 is protected such as with Boc2O and DMAP in CH2Cl2 at a temperature of about RT, to give the protected 6-nitro-2-hydroindazol-3-one. The protected 6-nitro-2-hydroindazol-3-one is reacted with an alcohol (wher...
10.6084/m9.figshare.5104873.v1
null
Nitro group.Nitro group
Primary amine.Primary amine
null
null
c1ccc2n[nH]cc2c1.c1ccc2n[nH]cc2c1
Other
[Pd]
null
null
O=[N+]([O-])c1ccc2c(Oc3n[nH]c4cc([N+](=O)[O-])ccc34)n[nH]c2c1>[Pd]>Nc1ccc2c(Oc3n[nH]c4cc(N)ccc34)n[nH]c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1587dd2df9244ca197ae4e1bfe91ec4e
O=[N+]([O-])N1CCc2ccccc21>>NN1CCc2ccccc21
[N+](=O)([O-])N1CCC2=CC=CC=C12>>NN1CCC2=CC=CC=C12
O=[N+:1]([O-])[N:2]1[CH2:3][CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]21>>[NH2:1][N:2]1[CH2:3][CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]21
O=[N+]([O-])N1CCc2ccccc21
NN1CCc2ccccc21
null
[Pd]
null
Reduction
Reduction of nitro groups to amines
6bdc5b1d5c26702b9b2e2eba8a212ecfef1796cf7dff1d3c4aa29ea829bd6927
551d4b973c04e11a26a7d28f2bf46da71be13045335ec714830e5dd800ddb646
c1ccc2c(c1)CCN2
O=[N+;H0;D3:1](-[O-])-[#7:2](-[C:3])-[c:4]>>[C:3]-[#7:2](-[NH2;D1;+0:1])-[c:4]
null
[]
null
null
null
null
Substituted indolines 51 are prepared such as by the procedures described in Scheme 15. Substituted amino-indolines 48 are prepared from the nitroindoline 46 and a ketone in the presence of NaHB(OAc)3 to form the 1-substituted indoline 47. The nitroindoline 47 is hydrogenated, such as with H2 in the presence of a catal...
10.6084/m9.figshare.5104873.v1
null
Hydrazine
Hydrazine
null
null
c1ccc2c(c1)CC[NH]2
Other
[Pd]
null
null
O=[N+]([O-])N1CCc2ccccc21>[Pd]>NN1CCc2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a4f37722ccab48ea9c643fffa08d8fae
COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1>>O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1
COC1=CC(=CC(=C1)C(F)(F)F)[N+](=O)[O-].Cl.N1=CC=CC=C1>>[N+](=O)([O-])C=1C=C(C=C(C1)C(F)(F)F)O
C[O:7][c:6]1[cH:5][c:4]([N+:2](=[O:1])[O-:3])[cH:14][c:9]([C:10]([F:11])([F:12])[F:13])[cH:8]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6]([OH:7])[cH:8][c:9]([C:10]([F:11])([F:12])[F:13])[cH:14]1
COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccccc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
210
CELSIUS
null
null
1-Methoxy-3-nitro-5-trifluoromethyl-benzene (10 g, Aldrich) and pyridine-HCl (41.8 g, Aldrich) were mixed together and heated neat at 210° C. in an open flask. After 2.5 h the mixture was cooled to RT and partitioned between 1N HCl and EtOAc. The EtOAc fraction was washed with 1N HCl (4×), brine (1×), dried with Na2SO4...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1
Other
null
210
null
COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1>>O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fa7e02be9189472e85b9f9a365326929
CC(C)(C)OC(=O)N1CCC(O)CC1.O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1>>CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1
C(=O)(OC(C)(C)C)N1CCC(CC1)O.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.[N+](=O)([O-])C=1C=C(C=C(C1)C(F)(F)F)O.CCOC(=O)/N=N/C(=O)OCC>>C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)[N+](=O)[O-]
O[CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:27][CH2:26]1.[OH:12][c:13]1[cH:14][c:15]([N+:16](=[O:17])[O-:18])[cH:19][c:20]([C:21]([F:22])([F:23])[F:24])[cH:25]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([N+:16](=[O:17...
CC(C)(C)OC(=O)N1CCC(O)CC1.O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1
CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[c:9]:[c:8](-[O;H0;D2;+0:7]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:10]
null
[]
-20
CELSIUS
8
HOUR
3-Nitro-5-trifluoromethyl-phenol (8.81 g) was dissolved in THF (76 ml). 1-Boc-4-hydroxy-piperidine (8.81 g, Aldrich) and Ph3P (11.15 g) were added and the solution was cooled to −20° C. A solution of DEAD (6.8 ml, Aldrich) in THF (36 ml) was added dropwise, maintaining the temperature between −20 and −10° C. The reacti...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1
HO-
C1CCOC1
-20
8
CC(C)(C)OC(=O)N1CCC(O)CC1.O=[N+]([O-])c1cc(O)cc(C(F)(F)F)c1>C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-db81e4b54a584baba88fec296194d0d9
CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1
C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)[N+](=O)[O-]>>C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)N
O=[N+:16]([O-])[c:15]1[cH:14][c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:25][CH2:24]2)[cH:23][c:18]([C:19]([F:20])([F:21])[F:22])[cH:17]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([NH2:16])[cH:17][c:18]([C...
CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1
null
[Pd]
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(OC2CCNCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine (470 mg) was dissolved in MeOH (12 ml) and Pd/C (10 mg) was added. After sparging briefly with H2, the mixture was stirred under H2 for 6H. The catalyst was removed by filtration and the MeOH solution was concentrated in vacuo to yield 1-Boc-4-(3-amino-5-trifluorom...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1CC[NH]CC1.c1ccccc1
Other
[Pd].CO
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1>[Pd].CO>CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a950f58865714d7fa987025e113fc383
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1F>>CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1
CCOC(=O)C.CCCCCC.C(=O)(O)[O-].[Na+].C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)N.FC1=NC=CC=C1C(=O)Cl>>C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)F
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([NH2:16])[cH:26][c:27]([C:28]([F:29])([F:30])[F:31])[cH:32]2)[CH2:33][CH2:34]1.Cl[C:17](=[O:18])[c:19]1[cH:20][cH:21][cH:22][n:23][c:24]1[F:25]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][C...
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1F
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1
null
null
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(Nc1cccc(OC2CCNCC2)c1)c1cccnc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[F;D1;H0:6]):[#7;a:7]:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[F;D1;H0:6]-[c:5](:[#7;a:7]:[c:8]):[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:4]
null
[]
null
null
2.5
HOUR
1-Boc-4-(3-amino-5-trifluoromethyl-phenoxy)-piperidine (4.37 g) was dissolved in CH2Cl2 (100 ml) and NaHCO3 (2.4 g, Baker) was added. 2-Fluoropyridine-3-carbonyl chloride (2.12 g) was added an the reaction was stirred at RT for 2.5 h. The reaction was filtered and concentrated in vacuo to yield a yellow foam. (30%) EtO...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CC[NH]CC1.c1ccccc1.c1ccncc1
HCl
C(Cl)Cl
null
2.5
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1F>C(Cl)Cl>CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4d55ad2ea91547f6954487c0bae278e1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1Cl>>CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1
C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)N.ClC1=NC=CC=C1C(=O)Cl.C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)F>>C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)Cl
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([NH2:16])[cH:26][c:27]([C:28]([F:29])([F:30])[F:31])[cH:32]2)[CH2:33][CH2:34]1.Cl[C:17](=[O:18])[c:19]1[cH:20][cH:21][cH:22][n:23][c:24]1[Cl:25]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][...
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1Cl
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(Nc1cccc(OC2CCNCC2)c1)c1cccnc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[Cl;D1;H0:6]):[#7;a:7]:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[Cl;D1;H0:6]-[c:5](:[#7;a:7]:[c:8]):[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:4]
null
[]
null
null
null
null
1-Boc-4-{3-[(2-chloro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxy}-piperidine was prepared from 1-Boc-4-(3-amino-5-trifluoromethyl-phenoxy)-piperidine and 2-chloropyridine-3-carbonyl chloride by a procedure similar to that described in the preparation of 1-Boc-4-{3-[(2-fluoro-pyridine-3-carbonyl)-amino]-5-tri...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CC[NH]CC1.c1ccccc1.c1ccncc1
HCl
null
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1.O=C(Cl)c1cccnc1Cl>>CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-facb0e23ce574bfe9a9cd300c9825163
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1.CC(C)(C)OC(=O)N1CCCC1COc1cc(N)cc(C(F)(F)F)c1>>CC(C)(C)OC(=O)N1CCCC1COc1cc(NC(=O)c2cccnc2F)cc(C(F)(F)F)c1
C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)F.C(=O)(OC(C)(C)C)N1C(CCC1)COC1=CC(=CC(=C1)C(F)(F)F)N>>C(=O)(OC(C)(C)C)N1C(CCC1)COC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)F
CC(C)(C)OC(=O)N1CCC(Oc2cc(N[C:19](=[O:20])[c:21]3[cH:22][cH:23][cH:24][n:25][c:26]3[F:27])cc(C(F)(F)F)c2)CC1.[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:13][O:14][c:15]1[cH:16][c:17]([NH2:18])[cH:28][c:29]([C:30]([F:31])([F:32])[F:33])[cH:34]1>>[CH3:1][C:2]([CH3:3])([CH3:4]...
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1.CC(C)(C)OC(=O)N1CCCC1COc1cc(N)cc(C(F)(F)F)c1
CC(C)(C)OC(=O)N1CCCC1COc1cc(NC(=O)c2cccnc2F)cc(C(F)(F)F)c1
null
null
null
Acylation
OtherReaction
4a154f3d0451f7adc7e06eb20420593d6aae77ff8199bbf6d044af104e3f431a
3a1146f373e13aeeb4978d04787fef10d7913789488cc4629f5b8b7a8a42f296
O=C(Nc1cccc(OCC2CCCN2)c1)c1cccnc1
C-C(-C)(-C)-O-C(=O)-N1-C-C-C(-O-c2:c:c(-N-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[F;D1;H0:6]):[#7;a:7]:[c:8]):c:c(-C(-F)(-F)-F):c:2)-C-C-1.[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[F;D1;H0:6]-[c:5](:[#7;a:7]:[c:8]):[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:4]
null
[]
null
null
null
null
1-Boc-2-{3-[(2-Fluoro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxymethyl}-pyrrolidine was prepared from 1-Boc-2-(3-amino-5-trifluoromethyl-phenoxymethyl)-pyrrolidine by a procedure similar to that described in the preparation of 1-Boc-4-{3-[(2-fluoro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxy}-piper...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Carbamic ester.Ether.Ether.Secondary amide.Primary amine.Boc
Secondary amide
C1CCNCC1.c1ccccc1
null
C1CC[NH]C1.c1ccccc1.c1ccncc1
HF
null
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3F)cc(C(F)(F)F)c2)CC1.CC(C)(C)OC(=O)N1CCCC1COc1cc(N)cc(C(F)(F)F)c1>>CC(C)(C)OC(=O)N1CCCC1COc1cc(NC(=O)c2cccnc2F)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5acee4ef974a4b6c981b26380a571c62
CC(C)(C)OC(=O)N1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1>>O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1
C(=O)(OC(C)(C)C)N1C(CCC1)COC1=CC(=CC(=C1)C(F)(F)F)[N+](=O)[O-].C(=O)(C(F)(F)F)O>>[N+](=O)([O-])C=1C=C(OCC2NCCC2)C=C(C1)C(F)(F)F
CC(C)(C)OC(=O)[N:13]1[CH:9]([CH2:8][O:7][c:6]2[cH:5][c:4]([N+:2](=[O:1])[O-:3])[cH:20][c:15]([C:16]([F:17])([F:18])[F:19])[cH:14]2)[CH2:10][CH2:11][CH2:12]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6]([O:7][CH2:8][CH:9]2[CH2:10][CH2:11][CH2:12][NH:13]2)[cH:14][c:15]([C:16]([F:17])([F:18])[F:19])[cH:20]1
CC(C)(C)OC(=O)N1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
7b506000be0005f6be41b2386b5bd6a8c45f704baa22d692d2f2ec984758e4ad
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(OCC2CCCN2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C:6]>>[C:6]-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
1
HOUR
1-Boc-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine (2.35 g) was dissolved in CH2Cl2 (60 ml) and TFA (20 ml) was added. After stirring for 1 h at RT, the mixture was concentrated in vacuo to yield 2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine as an oil that solidified upon standing. The material was...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]C1
C1CCNC1
c1ccccc1.C1CCNC1
HO-
C(Cl)Cl
null
1
CC(C)(C)OC(=O)N1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1>C(Cl)Cl>O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a424300cf364497ebc9bd7e8f2623081
C=O.O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1>>CN1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
CC(=O)O.C=O.[N+](=O)([O-])C=1C=C(OCC2NCCC2)C=C(C1)C(F)(F)F.[BH3-]C#N.[Na+]>>CN1C(CCC1)COC1=CC(=CC(=C1)C(F)(F)F)[N+](=O)[O-]
O=[CH2:1].[NH:2]1[CH2:3][CH2:4][CH2:5][CH:6]1[CH2:7][O:8][c:9]1[cH:10][c:11]([N+:12](=[O:13])[O-:14])[cH:15][c:16]([C:17]([F:18])([F:19])[F:20])[cH:21]1>>[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]1[CH2:7][O:8][c:9]1[cH:10][c:11]([N+:12](=[O:13])[O-:14])[cH:15][c:16]([C:17]([F:18])([F:19])[F:20])[cH:21]1
C=O.O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1
CN1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
null
null
CC#N
Functional Group Addition
Eschweiler-Clarke Secondary Amine Methylation
596806345838051e870a8f6bc98ea80fe70c98a5e33506938d4dd972c4e2862a
68e600b2a07b08da0e807cdaeea0a42b844f72be0a4c3ae081bd557e5f2bfd2d
c1ccc(OCC2CCCN2)cc1
O=[CH2;D1;+0:1].[C:2]-[C:3]1-[C:4]-[C:5]-[C:6]-[NH;D2;+0:7]-1>>[C:2]-[C:3]1-[C:4]-[C:5]-[C:6]-[N;H0;D3;+0:7]-1-[CH3;D1;+0:1]
null
[]
null
null
45
MINUTE
2-(3-Nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine (6 mmol) was dissolved in CH3CN (20 ml) and formaldehyde (2.4 ml, 37% aqueous) was added. NaBH3CN (607 mg) was added, an exotherm was observed. The pH is monitored every 15 min and adjusted to ˜7 with AcOH. After 45 min, the mixture was concentrated in vacuo and t...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1
Other
CC#N
null
0.75
C=O.O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1>CC#N>CN1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-79e9e6ff8dd14b82b6e33e56e284dd72
CC(C)(C)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]>>CC(C)(C)c1ccc(N)cc1[N+](=O)[O-]
[S].[N+](=O)([O-])C1=CC(=C(C=C1)C(C)(C)C)[N+](=O)[O-]>>C(C)(C)(C)C1=C(C=C(C=C1)N)[N+](=O)[O-]
O=[N+:9]([O-])[c:8]1[cH:7][cH:6][c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[c:11]([N+:12](=[O:13])[O-:14])[cH:10]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:10][c:11]1[N+:12](=[O:13])[O-:14]
CC(C)(C)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
CC(C)(C)c1ccc(N)cc1[N+](=O)[O-]
null
null
O
Functional Group Interconversion
Reduction of nitro groups to amines
5c1ea979989295c14f1f65f49e58974d5c524451abca65fc2e6cec44e3d0784f
10b8579fd1662beac4350d758bc16e1f45ee6ea295ff9572db62110c9e2a77db
c1ccccc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
A mixture of 1,3-dinitro-4-tert-butylbenzene (10.0 g) in H2O (56 ml) was heated to reflux. A mixture of Na2S (21.42 g) and sulfur (2.85 g) in H2O (34 ml) was added over 1 h via an addition funnel. The reaction maintained at reflux for 1.5 h then cooled to RT and extracted with EtOAc. The organic extracts were combined ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1
Other
O
null
null
CC(C)(C)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]>O>CC(C)(C)c1ccc(N)cc1[N+](=O)[O-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6889494b13bd4ce1a70acbee562ea485
CC(=O)OC(C)=O.Nc1cc(Br)cc(C(F)(F)F)c1>>CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1
BrC=1C=C(C=C(C1)C(F)(F)F)N.CC(=O)OC(=O)C.O>>BrC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O
CC(=O)O[C:2]([CH3:1])=[O:3].[NH2:4][c:5]1[cH:6][c:7]([Br:8])[cH:9][c:10]([C:11]([F:12])([F:13])[F:14])[cH:15]1>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][c:7]([Br:8])[cH:9][c:10]([C:11]([F:12])([F:13])[F:14])[cH:15]1
CC(=O)OC(C)=O.Nc1cc(Br)cc(C(F)(F)F)c1
CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1
null
null
CC(=O)O
Acylation
Aminolysis of esters
87d35e51b477fc9a658a6f307eb56d84c8879182772c9dd3a42ec0d584fd2684
627cbc0550c9f51ad0105d9fcf46677e8c93bed87ee95bfe69292a82550c95b7
c1ccccc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[NH2;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[NH;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
8
HOUR
3-Bromo-5-(trifluoromethyl)phenylamine (5 g, Alfa-Aesar) was dissolved in AcOH (140 ml) and Ac2O (5.9 ml, Aldrich) was added. The reaction was stirred at RT overnight. The mixture was added slowly to H2O (˜700 ml) forming a white precipitate. The solid was isolated by filtration, washed with H2O and dried under vacuum ...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Secondary amide
null
null
c1ccccc1
HO-
CC(=O)O
null
8
CC(=O)OC(C)=O.Nc1cc(Br)cc(C(F)(F)F)c1>CC(=O)O>CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4d1ba4a1429b456fb24b0ac71be3ca02
CC(=O)Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1>>Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1
N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O.Cl>>N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)N
CC(=O)[NH:1][c:2]1[cH:3][c:4]([CH2:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][c:15]([C:16]([F:17])([F:18])[F:19])[cH:20]1>>[NH2:1][c:2]1[cH:3][c:4]([CH2:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][c:15]([C:16]([F:17])([F:18])[F:19])[cH:20]1
CC(=O)Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1
Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1
null
null
CCO
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
c1ccc(CCCN2CCCCC2)cc1
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
70
CELSIUS
8
HOUR
N-[3-(3-Piperidin-1-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide (1.33 g) was dissolved in EtOH (40 ml) and 12 N HCl (40 ml) was added. After stirring overnight at 70° C. and RT, the mixture was concentrated in vacuo, affording 3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenylamine as a brown oil. Conditions: See ...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccccc1.C1CC[NH]CC1
HO-
CCO
70
8
CC(=O)Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1>CCO>Nc1cc(CCCN2CCCCC2)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-12d9fdeda79849ceaaead73b998a6d10
CC(C)(C)OC(=O)N1CCC(CN2CC(C)(C)c3ccc([N+](=O)[O-])cc32)CC1>>CC1(C)CN(CC2CCNCC2)c2cc([N+](=O)[O-])ccc21
CC1(CN(C2=CC(=CC=C12)[N+](=O)[O-])CC1CCN(CC1)C(=O)OC(C)(C)C)C>>CC1(CN(C2=CC(=CC=C12)[N+](=O)[O-])CC1CCNCC1)C
CC(C)(C)OC(=O)[N:10]1[CH2:9][CH2:8][CH:7]([CH2:6][N:5]2[CH2:4][C:2]([CH3:1])([CH3:3])[c:21]3[c:13]2[cH:14][c:15]([N+:16](=[O:17])[O-:18])[cH:19][cH:20]3)[CH2:12][CH2:11]1>>[CH3:1][C:2]1([CH3:3])[CH2:4][N:5]([CH2:6][CH:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH2:12]2)[c:13]2[cH:14][c:15]([N+:16](=[O:17])[O-:18])[cH:19][cH:20][...
CC(C)(C)OC(=O)N1CCC(CN2CC(C)(C)c3ccc([N+](=O)[O-])cc32)CC1
CC1(C)CN(CC2CCNCC2)c2cc([N+](=O)[O-])ccc21
null
null
Cl.CCOC(=O)C
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc2c(c1)CCN2CC1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
null
[]
null
null
2
HOUR
3,3-Dimethyl-1-(1-Boc-piperidin-4-ylmethyl)-6-nitro-2,3-dihydro-1H-indole was dissolved in HCl/EtOAc and stirred for 2 h. The mixture was concentrated in vacuo and partitioned between 1,2-dichloroethane and 1N NaOH. The organic layer was removed, washed with brine, dried (Na2SO4) and filtered. The material was used wit...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
C1CCNCC1.c1ccc2c(c1)CC[NH]2
HO-
Cl.CCOC(=O)C
null
2
CC(C)(C)OC(=O)N1CCC(CN2CC(C)(C)c3ccc([N+](=O)[O-])cc32)CC1>Cl.CCOC(=O)C>CC1(C)CN(CC2CCNCC2)c2cc([N+](=O)[O-])ccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2ea737714a754007ad2eb13654ea3835
C=CCN1CCOCC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1>>CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
C(C=C)N1CCOCC1.BrC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O.N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O>>N1(CCOCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O
[CH2:8]=[CH:9][CH2:10][N:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1.Br[c:7]1[cH:6][c:5]([NH:4][C:2]([CH3:1])=[O:3])[cH:23][c:18]([C:19]([F:20])([F:21])[F:22])[cH:17]1>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][c:7]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[cH:17][c:18]([C:19]([F:20])([F:21])[F...
C=CCN1CCOCC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1
CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
null
null
null
C-C Coupling
OtherReaction
2d4a44695e29e4a9ab430c3b66736ad86dd99247e7216f16f3ca137abca78747
df8442c9f2045421fb18548edb9c6acaeb9710f63e741d9f72e0000ca35c948a
c1ccc(CCCN2CCOCC2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[#7:6]-[C:7]-[CH;D2;+0:8]=[CH2;D1;+0:9]>>[#7:6]-[C:7]-[CH2;D2;+0:8]-[CH2;D2;+0:9]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
null
[]
null
null
null
null
N-[3-(3-Morpholin-4-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide was prepared from allyl morpholine and N-(3-bromo-5-trifluoromethyl-phenyl)-acetamide similar to that described in the preparation of N-[3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Allyl
null
c1ccccc1
c1ccccc1
c1ccccc1.C1COCC[NH]1
Br-
null
null
null
C=CCN1CCOCC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1>>CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bc47abb28d8643fba69d2f56ca33e44d
CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1>>Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)N.N1(CCOCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O>>N1(CCOCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)N
CC(=O)[NH:1][c:2]1[cH:3][c:4]([CH2:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[cH:14][c:15]([C:16]([F:17])([F:18])[F:19])[cH:20]1>>[NH2:1][c:2]1[cH:3][c:4]([CH2:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[cH:14][c:15]([C:16]([F:17])([F:18])[F:19])[cH:20]1
CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
null
null
null
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
c1ccc(CCCN2CCOCC2)cc1
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
3-(3-Morpholin-4-yl-propyl)-5-trifluoromethyl-phenylamine was prepared from N-[3-(3-morpholin-4-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide similar to that described in the preparation of 3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenylamine. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccccc1.C1COCC[NH]1
HO-
null
null
null
CC(=O)Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1>>Nc1cc(CCCN2CCOCC2)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1dd9fcd5907c45d0a728a79c728f030c
C=C1CCN(C)CC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1>>CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1
CN1CCC(CC1)=C.BrC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O.N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)NC(C)=O>>CN1CCC(CC1)C=1C=C(C=C(C1)C(F)(F)F)NC(C)=O
C=[C:8]1[CH2:9][CH2:10][N:11]([CH3:12])[CH2:13][CH2:14]1.Br[c:7]1[cH:6][c:5]([NH:4][C:2]([CH3:1])=[O:3])[cH:21][c:16]([C:17]([F:18])([F:19])[F:20])[cH:15]1>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][c:7]([CH:8]2[CH2:9][CH2:10][N:11]([CH3:12])[CH2:13][CH2:14]2)[cH:15][c:16]([C:17]([F:18])([F:19])[F:20])[cH:21]1
C=C1CCN(C)CC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1
CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1
null
null
null
C-C Coupling
OtherReaction
993479cf39c04983afa148c3c4a2c6e5a7ee5fe5faa129754f7d6a55323bb504
4b186811a4930853b446d93d9faa39b267bddb9ce0b8021bda5c5a3b2bc69f0b
c1ccc(C2CCNCC2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].C=[C;H0;D3;+0:6]1-[C:7]-[C:8]-[#7:9]-[C:10]-[C:11]-1>>[c:3]:[c:2]:[c;H0;D3;+0:1](-[CH;D3;+0:6]1-[C:7]-[C:8]-[#7:9]-[C:10]-[C:11]-1):[c:4]:[c:5]
null
[]
null
null
null
null
N-[3-(1-Methylpiperidin-4-yl)-5-trifluoromethyl-phenyl]-acetamide was prepared from 1-methyl-4-methylene-piperidine and N-(3-bromo-5-trifluoromethyl-phenyl)-acetamide similar to that described in the preparation of N-[3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide. Conditions: See reaction.notes.proced...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Vinyl
null
C1CC[NH]CC1.c1ccccc1
c1ccccc1.C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HBr
null
null
null
C=C1CCN(C)CC1.CC(=O)Nc1cc(Br)cc(C(F)(F)F)c1>>CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ba17c1c4d7f743a0b43c6abc06e718a6
CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1>>CN1CCC(c2cc(N)cc(C(F)(F)F)c2)CC1
N1(CCCCC1)CCCC=1C=C(C=C(C1)C(F)(F)F)N.CN1CCC(CC1)C=1C=C(C=C(C1)C(F)(F)F)NC(C)=O>>CN1CCC(CC1)C=1C=C(C=C(C1)C(F)(F)F)N
CC(=O)[NH:9][c:8]1[cH:7][c:6]([CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:18][CH2:17]2)[cH:16][c:11]([C:12]([F:13])([F:14])[F:15])[cH:10]1>>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([c:6]2[cH:7][c:8]([NH2:9])[cH:10][c:11]([C:12]([F:13])([F:14])[F:15])[cH:16]2)[CH2:17][CH2:18]1
CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1
CN1CCC(c2cc(N)cc(C(F)(F)F)c2)CC1
null
null
null
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
c1ccc(C2CCNCC2)cc1
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
3-(1-Methylpiperidin-4-yl)-5-trifluoromethyl-phenylamine was prepared from N-[3-(1-methylpiperidin-4-yl)-5-trifluoromethyl-phenyl]-acetamide similar to the procedure described in the preparation of 3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenylamine. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
C1CC[NH]CC1.c1ccccc1
HO-
null
null
null
CC(=O)Nc1cc(C2CCN(C)CC2)cc(C(F)(F)F)c1>>CN1CCC(c2cc(N)cc(C(F)(F)F)c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eaf46af33faf4d5d97da5970b4ed4fac
Cl>>Cl.Cl
CN1CCC(CC1)OC1=NC=CC(=C1)CN.Cl.CCOCC>>Cl.Cl.CN1CCC(CC1)OC1=NC=CC(=C1)CN
[ClH:17]>>[ClH:17].[ClH:18]
Cl
Cl.Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
null
null
null
null
[2-(1-Methylpiperidin-4-yloxy)-pyridin-4-yl]methylamine was diluted with Et2O (50 ml) and 1M HCl/Et2O (47 ml) was added. The vessel was swirled until precipitate formed. Conditions: See reaction.notes.procedure_details. Workup: was added; formed
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
Other
CCOCC
null
null
Cl>CCOCC>Cl.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-35c523bdd80c45beba839f8536d196ec
COC(=O)C(C)N1CCOCC1>>CC(CO)N1CCOCC1
[OH-].[Na+].[H-].[H-].[H-].[H-].[Li+].[Al+3].N#N.N1(CCOCC1)C(C(=O)OC)C>>N1(CCOCC1)C(CO)C
CO[C:3]([CH:2]([CH3:1])[N:5]1[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1)=[O:4]>>[CH3:1][CH:2]([CH2:3][OH:4])[N:5]1[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1
COC(=O)C(C)N1CCOCC1
CC(CO)N1CCOCC1
null
null
O.C1CCOC1
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C1COCCN1
C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3](-[#7:4])-[C;D1;H3:5]>>[#7:4]-[C:3](-[C;D1;H3:5])-[CH2;D2;+0:1]-[OH;D1;+0:2]
null
[]
0
CELSIUS
1
HOUR
LAH powder (1.6 g) was added to a flask while under N2 atmosphere, immediately followed by THF (50 ml). The mixture was chilled to 0° C., methyl 2-morpholin-4-yl-propionate (5 g) was added dropwise to the reaction mixture and stirred at 0° C. After 1 h, the mixture was worked up by adding H2O (44 mL), 2N NaOH (44 mL), ...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1COCC[NH]1
Other
O.C1CCOC1
0
1
COC(=O)C(C)N1CCOCC1>O.C1CCOC1>CC(CO)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a350655571c24bc38bae786d41339d9c
CC(C)(C)c1ccccc1N.O=[N+]([O-])[O-]>>CC(C)(C)c1ccc([N+](=O)[O-])cc1N
[N+](=O)([O-])[O-].[K+].OS(=O)(=O)O.C(C)(C)(C)C1=C(N)C=CC=C1.[N+](=O)([O-])[O-].[K+].BrC1=C(C(=O)N)C=CC=N1>>C(C)(C)(C)C1=C(N)C=C(C=C1)[N+](=O)[O-]
[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][cH:8][cH:12][c:13]1[NH2:14].[O-][N+:9](=[O:10])[O-:11]>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]1[NH2:14]
CC(C)(C)c1ccccc1N.O=[N+]([O-])[O-]
CC(C)(C)c1ccc([N+](=O)[O-])cc1N
null
null
O
Functional Group Addition
Aromatic nitration with NO3 salt
53848b8b2bb4e867226e49db2e60519b24be9379900e3ad7c56af54fe8fde7a5
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccccc1
[O-]-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[c:4]:[c:5]:[cH;D2;+0:6]:[c:7]:[c:8]>>[O;-;D1;H0:2]-[N+;H0;D3:1](=[O;D1;H0:3])-[c;H0;D3;+0:6](:[c:5]:[c:4]):[c:7]:[c:8]
null
[]
-10
CELSIUS
null
null
To H2SO4 (98%, 389 mL) in a 500 mL 3-neck flask was added 2-tert-butyl aniline (40.6 mL). The reaction was cooled to −10° C. and KNO3 in 3.89 g aliquots was added every 6 min for a total of 10 aliquots. Tried to maintain temperature at −5° C. to −10° C. After final addition of KNO3, stirred the reaction for five min th...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccccc1
c1ccccc1
c1ccccc1
HO-
O
-10
null
CC(C)(C)c1ccccc1N.O=[N+]([O-])[O-]>O>CC(C)(C)c1ccc([N+](=O)[O-])cc1N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-87e7bf417e8b4a33a1f5548ab4869f94
CC(C)(C)c1ccc([N+](=O)[O-])cc1N.O=S(=O)(O)O>>CC(C)(C)c1ccc([N+](=O)[O-])cc1O
OS(=O)(=O)O.C(C)(C)(C)C1=C(N)C=C(C=C1)[N+](=O)[O-].NC1=CC=CC=C1.NC(=O)N.N(=O)[O-].[Na+].N(=O)[O-].[Na+]>>C(C)(C)(C)C1=C(C=C(C=C1)[N+](=O)[O-])O
N[c:13]1[c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12]1.O=S(=O)(O)[OH:14]>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]1[OH:14]
CC(C)(C)c1ccc([N+](=O)[O-])cc1N.O=S(=O)(O)O
CC(C)(C)c1ccc([N+](=O)[O-])cc1O
null
null
O.CCOC(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
ea88ed7f3099519cddf317836afa8700324714e983b7b91a9a2b5fa238ea7972
0faab53fb44f5d790c940e8273c888214a6763f53a41b0c03d0241319b9333e9
c1ccccc1
N-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5]):[c:6].O-S(=O)(=O)-[OH;D1;+0:7]>>[C:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[OH;D1;+0:7]):[c:2]:[c:3]
null
[]
0
CELSIUS
null
null
In a 250 ml round bottom flask, 20 mL concentrated H2SO4 was added to 2-tert-butyl-5-nitro-aniline (7.15 g) by adding 5 mL aliquots of acid and sonicating with occasional heating until all of the starting aniline went into solution. H2O (84 ml) was added with stirring, then the reaction was cooled to 0° C. forming a ye...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Aromatic alcohol
c1ccccc1
c1ccccc1
c1ccccc1
HO-
O.CCOC(=O)C
0
null
CC(C)(C)c1ccc([N+](=O)[O-])cc1N.O=S(=O)(O)O>O.CCOC(=O)C>CC(C)(C)c1ccc([N+](=O)[O-])cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-518f6a5655754bf0a29299adb7606654
C=O.CCOC(=O)C1CCNCC1>>CCOC(=O)C1CCN(C)CC1
[BH3-]C#N.[Na+].C=O.C(C)(=O)O.C(C)OC(=O)C1CCNCC1>>C(C)OC(=O)C1CCN(CC1)C
O=[CH2:10].[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][NH:9][CH2:11][CH2:12]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][N:9]([CH3:10])[CH2:11][CH2:12]1
C=O.CCOC(=O)C1CCNCC1
CCOC(=O)C1CCN(C)CC1
null
null
CO
Heteroatom Alkylation and Arylation
Eschweiler-Clarke Secondary Amine Methylation
e23db47f33553519e7237e30c3b19a21fcbb90bde44fbb5566021920bc9b7164
e1fdef8fde1c506d7c9deb8fd5e6f322eceea2abce3167abcf412a1fa4fd5443
C1CCNCC1
O=[CH2;D1;+0:1].[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]>>[C:2]-[C:3]-[N;H0;D3;+0:4](-[CH3;D1;+0:1])-[C:5]-[C:6]
null
[]
0
CELSIUS
2
HOUR
Piperidine-4-carboxylic acid ethyl ester (78 g) was dissolved in MeOH (1.2 L) at RT then formaldehyde (37%, 90 ml) and acetic acid (42 ml) were added and stirred for 2 h. The mixture was cooled to 0° C., NaCNBH3 (70 g) was added, and the mix was stirred for 20 min at 0° C., then overnight at RT. The mixture was cooled ...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1
Other
CO
0
2
C=O.CCOC(=O)C1CCNCC1>CO>CCOC(=O)C1CCN(C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b0dfe7bd1633448ea55de33fb70307fb
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1.CN1CCC(COc2cc(N)ccc2C(C)(C)C)CC1>>CN1CCC(COc2cc(NC(=O)c3cccnc3Cl)ccc2C(C)(C)C)CC1
C(=O)(OC(C)(C)C)N1CCC(CC1)OC1=CC(=CC(=C1)C(F)(F)F)NC(=O)C=1C(=NC=CC1)Cl.C(C)(C)(C)C1=C(C=C(C=C1)N)OCC1CCN(CC1)C>>C(C)(C)(C)C1=C(C=C(C=C1)NC(C1=C(N=CC=C1)Cl)=O)OCC1CCN(CC1)C
CC(C)(C)OC(=O)N1CCC(Oc2cc(N[C:12](=[O:13])[c:14]3[cH:15][cH:16][cH:17][n:18][c:19]3[Cl:20])cc(C(F)(F)F)c2)CC1.[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([CH2:6][O:7][c:8]2[cH:9][c:10]([NH2:11])[cH:21][cH:22][c:23]2[C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28][CH2:29]1>>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([CH2:6][O:7][c:8]2[cH:9][c:...
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1.CN1CCC(COc2cc(N)ccc2C(C)(C)C)CC1
CN1CCC(COc2cc(NC(=O)c3cccnc3Cl)ccc2C(C)(C)C)CC1
null
null
null
Acylation
OtherReaction
4a154f3d0451f7adc7e06eb20420593d6aae77ff8199bbf6d044af104e3f431a
3a1146f373e13aeeb4978d04787fef10d7913789488cc4629f5b8b7a8a42f296
O=C(Nc1cccc(OCC2CCNCC2)c1)c1cccnc1
C-C(-C)(-C)-O-C(=O)-N1-C-C-C(-O-c2:c:c(-N-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[Cl;D1;H0:6]):[#7;a:7]:[c:8]):c:c(-C(-F)(-F)-F):c:2)-C-C-1.[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[Cl;D1;H0:6]-[c:5](:[#7;a:7]:[c:8]):[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:4]
null
[]
null
null
null
null
N-[4-tert-Butyl-3-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-2-chloro-nicotinamide was prepared from 4-tert-butyl-3-(1-methyl-piperidin-4-ylmethoxy)-phenylamine by a procedure similar to that described in the preparation of 1-Boc-4-{3-[(2-chloro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxy}-piperidine. Condition...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Carbamic ester.Ether.Ether.Secondary amide.Primary amine.Boc
Secondary amide
C1CCNCC1.c1ccccc1
null
C1CC[NH]CC1.c1ccccc1.c1ccncc1
HF
null
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(NC(=O)c3cccnc3Cl)cc(C(F)(F)F)c2)CC1.CN1CCC(COc2cc(N)ccc2C(C)(C)C)CC1>>CN1CCC(COc2cc(NC(=O)c3cccnc3Cl)ccc2C(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fb20fce2f941404db1e761c7c0fc4015
CC(C)(C)c1ccc([N+](=O)[O-])cc1O.ClCCN1CCCCC1>>CC(C)(C)c1ccc([N+](=O)[O-])cc1OCCN1CCCCC1
Cl.ClCCN1CCCCC1.C(=O)([O-])[O-].[K+].[K+].Cl.ClCCN1CCCCC1.C(C)(C)(C)C1=C(C=C(C=C1)[N+](=O)[O-])O.C(=O)([O-])[O-].[K+].[K+].CC(=O)C>>C(C)(C)(C)C1=C(OCCN2CCCCC2)C=C(C=C1)[N+](=O)[O-]
[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]1[OH:14].Cl[CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]1[O:14][CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][CH2:20][CH2:21][...
CC(C)(C)c1ccc([N+](=O)[O-])cc1O.ClCCN1CCCCC1
CC(C)(C)c1ccc([N+](=O)[O-])cc1OCCN1CCCCC1
null
CCCC[N+](CCCC)(CCCC)CCCC.[I-]
O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(OCCN2CCCCC2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[#7:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
null
null
To 2-tert-butyl-5-nitrophenol (1.01 g) and K2CO3 (1.72 g) was added acetone (35 ml) and H2O (10.5 mL), then 1-(2-chloroethyl)piperidine HCl (1.909 g) and TBAI (153 mg). The mixture was stirred at reflux overnight. Additional K2CO3 (850 mg) and 1-(2-chloroethyl)-piperidine HCl (950 mg) were added and the mixture was hea...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1CC[NH]CC1
HCl
CCCC[N+](CCCC)(CCCC)CCCC.[I-].O
null
null
CC(C)(C)c1ccc([N+](=O)[O-])cc1O.ClCCN1CCCCC1>CCCC[N+](CCCC)(CCCC)CCCC.[I-].O>CC(C)(C)c1ccc([N+](=O)[O-])cc1OCCN1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-853468a647964592914fef55bd0ff766
CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(CO)CC1
N1(CCOCC1)C(CO)C.C(C)OC(=O)C1CCN(CC1)C(=O)OC(C)(C)C>>C(=O)(OC(C)(C)C)N1CCC(CC1)CO
CCO[C:12]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:15][CH2:14]1)=[O:13]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([CH2:12][OH:13])[CH2:14][CH2:15]1
CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(CO)CC1
null
null
null
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C1CCNCC1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3](-[C:4])-[C:5]>>[C:4]-[C:3](-[CH2;D2;+0:1]-[OH;D1;+0:2])-[C:5]
null
[]
null
null
null
null
1-Boc-4-Hydroxymethyl-piperidine was prepared from 1-Boc-piperidine-4-carboxylic acid ethyl ester by a procedure similar to that described in the preparation of 2-morpholin-4-yl-propanol. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1CC[NH]CC1
HO-
null
null
null
CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(CO)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cd9bf937214e44e297797d92cd6baeda
CC(C)(C)OC(=O)N1CCC(CO)CC1.CS(=O)(=O)Cl>>CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1
C(=O)(OC(C)(C)C)N1CCC(CC1)CO.S(=O)(=O)(C)Cl>>C(=O)(OC(C)(C)C)N1CCC(CC1)COS(=O)(=O)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([CH2:12][OH:13])[CH2:18][CH2:19]1.Cl[S:14]([CH3:15])(=[O:16])=[O:17]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([CH2:12][O:13][S:14]([CH3:15])(=[O:16])=[O:17])[CH2:18][CH2:19]1
CC(C)(C)OC(=O)N1CCC(CO)CC1.CS(=O)(=O)Cl
CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1
null
null
C(Cl)Cl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
C1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
null
[]
0
CELSIUS
15
MINUTE
Dissolved 1-Boc-4-hydroxymethyl-piperidine in anhydrous CH2Cl2 (50 ml) and TEA (4.5 ml) and cooled to 0° C. Mesyl chloride (840 μl) was added and the mixture was stirred for 15 min then at RT for 45 min. The mixture was washed with brine/1N HCl and then brine, dried over Na2SO4, concentrated in vacuo and dried under hi...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
C1CC[NH]CC1
HCl
C(Cl)Cl
0
0.25
CC(C)(C)OC(=O)N1CCC(CO)CC1.CS(=O)(=O)Cl>C(Cl)Cl>CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5e253cb8a1ef4c40a26bddd3bc156d38
CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1>>CC(C)(C)OC(=O)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
C(=O)([O-])[O-].[K+].[K+].[H-].[Na+].[N+](=O)([O-])C=1C=CC(=C(C1)O)C(C(F)(F)F)(F)F.C(=O)(OC(C)(C)C)N1CCC(CC1)COS(=O)(=O)C>>C(=O)(OC(C)(C)C)N1CCC(CC1)COC1=CC(=CC=C1C(C(F)(F)F)(F)F)[N+](=O)[O-]
CS(=O)(=O)O[CH2:12][CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:31][CH2:30]1.[OH:13][c:14]1[cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][cH:21][c:22]1[C:23]([F:24])([F:25])[C:26]([F:27])([F:28])[F:29]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([CH...
CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1
CC(C)(C)OC(=O)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
null
null
CN(C)C=O.[OH-].[Na+]
Heteroatom Alkylation and Arylation
OtherReaction
57201f1afbda3b7775282ca8e3c59a4fb8e542f888bbdbfa994f08238598f88e
b300ae9ac00448343b04f8595ac10c40ddc175401f75ad1a9cb423839305bb59
c1ccc(OCC2CCNCC2)cc1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C:3]-[C:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8])-[C:4]
null
[]
null
null
10
MINUTE
To a slurry of 60% NaH suspension in DMF (30 mL) at RT added a solution of 5-nitro-2-pentafluoroethyl-phenol (3.6 g) in 5 mL DMF. The dark red mixture was stirred at RT for 10 min then added a solution of 1-Boc-4-methylsulfonyloxymethyl-piperidine (3.1 g) in 5 mL DMF. The reaction was stirred at 60° C. and 95° C. After...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Aromatic alcohol
Ether
null
null
C1CC[NH]CC1.c1ccccc1
MsOH.HO-
CN(C)C=O.[OH-].[Na+]
null
0.166667
CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1>CN(C)C=O.[OH-].[Na+]>CC(C)(C)OC(=O)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b2f37b5b369a4619a6d6a65e13db82a6
CC(C)=O.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCC2CCNCC2)c1>>CC(C)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
CC(=O)O.[N+](=O)([O-])C=1C=CC(=C(OCC2CCNCC2)C1)C(C(F)(F)F)(F)F.CC(=O)C.CC(=O)C.[BH-](OC(=O)C)(OC(=O)C)OC(=O)C.[Na+]>>C(C)(C)N1CCC(CC1)COC1=C(C=CC(=C1)[N+](=O)[O-])C(C(F)(F)F)(F)F
O=[C:2]([CH3:1])[CH3:3].[NH:4]1[CH2:5][CH2:6][CH:7]([CH2:8][O:9][c:10]2[cH:11][c:12]([N+:13](=[O:14])[O-:15])[cH:16][cH:17][c:18]2[C:19]([F:20])([F:21])[C:22]([F:23])([F:24])[F:25])[CH2:26][CH2:27]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([CH2:8][O:9][c:10]2[cH:11][c:12]([N+:13](=[O:14])[O-:15])[cH:16][cH:17]...
CC(C)=O.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCC2CCNCC2)c1
CC(C)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
null
null
ClCCCl
Functional Group Addition
reductive amination
bdf3492dbea0a0e2fa2b9241cf6ccf0c5df69a797c0b4efc848998d30aeb7af2
2cf44c818c8ccfe8470f14fa07c7828891879f6644e8064bb35acc17d9c36b54
c1ccc(OCC2CCNCC2)cc1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:4]-[C:5]-[N;H0;D3;+0:6](-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3])-[C:7]-[C:8]
null
[]
null
null
8
HOUR
Dissolved 4-(5-nitro-2-pentafluoroethyl-phenoxymethyl)-piperidine (646 mg) in 1,2-dichloroethane (6.4 ml), then added acetone (136 ul), NaBH(OAc)3 (541 mg) and finally AcOH (105 ul). Stirred the cloudy yellow solution under N2 at RT overnight. Added another 130 uL acetone and stirred at RT over weekend. Quenched the re...
10.6084/m9.figshare.5104873.v1
null
Ketone.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1
Other
ClCCCl
null
8
CC(C)=O.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCC2CCNCC2)c1>ClCCCl>CC(C)N1CCC(COc2cc([N+](=O)[O-])ccc2C(F)(F)C(F)(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-51b3d1c1510e42a1b9e36193df81d854
ClCCN1CCCC1.O=[N+]([O-])c1ccc(C(F)(F)F)c(O)c1>>O=[N+]([O-])c1ccc(C(F)(F)F)c(OCCN2CCCC2)c1
[N+](=O)([O-])C=1C=CC(=C(C1)O)C(F)(F)F.ClCCN1CCCC1.C(C)(C)(C)C1=C(OCCN2CCCCC2)C=C(C=C1)[N+](=O)[O-]>>[N+](=O)([O-])C=1C=CC(=C(OCCN2CCCC2)C1)C(F)(F)F
Cl[CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][CH2:19][CH2:20]1.[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([C:8]([F:9])([F:10])[F:11])[c:12]([OH:13])[cH:21]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([C:8]([F:9])([F:10])[F:11])[c:12]([O:13][CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)[cH:21]1
ClCCN1CCCC1.O=[N+]([O-])c1ccc(C(F)(F)F)c(O)c1
O=[N+]([O-])c1ccc(C(F)(F)F)c(OCCN2CCCC2)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(OCCN2CCCC2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[#7:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
null
null
1-[2-(5-Nitro-2-trifluoromethylphenoxy)ethyl]-pyrrolidine was prepared from 5-nitro-2-trifluoromethyl-phenol and 1-(2-chloroethyl)pyrrolidine by a procedure similar to that described for 1-[2-(2-tert-butyl-5-nitro-phenoxy)-ethyl]-piperidine. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1CC[NH]C1
HCl
null
null
null
ClCCN1CCCC1.O=[N+]([O-])c1ccc(C(F)(F)F)c(O)c1>>O=[N+]([O-])c1ccc(C(F)(F)F)c(OCCN2CCCC2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ab3ee8f68a3e491d923b90186319c016
ClCCN1CCCCC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1>>O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCCN2CCCCC2)c1
[N+](=O)([O-])C=1C=CC(=C(C1)O)C(C(F)(F)F)(F)F.ClCCN1CCCCC1.C(C)(C)(C)C1=C(OCCN2CCCCC2)C=C(C=C1)[N+](=O)[O-]>>[N+](=O)([O-])C=1C=CC(=C(OCCN2CCCCC2)C1)C(C(F)(F)F)(F)F
Cl[CH2:17][CH2:18][N:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1.[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([C:8]([F:9])([F:10])[C:11]([F:12])([F:13])[F:14])[c:15]([OH:16])[cH:25]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([C:8]([F:9])([F:10])[C:11]([F:12])([F:13])[F:14])[c:15]([O:16][CH2:17][CH2:18][N:19]2[CH2:2...
ClCCN1CCCCC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1
O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCCN2CCCCC2)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(OCCN2CCCCC2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[#7:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
null
null
1-[2-(5-Nitro-2-pentafluoroethyl-phenoxy)-ethyl]-piperidine was prepared from 5-nitro-2-pentafluoroethylphenol and 1-(2-chloroethyl)piperidine by a procedure similar to that described in the preparation of 1-[2-(2-tert-butyl-5-nitro-phenoxy)-ethyl]-piperidine. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1CC[NH]CC1
HCl
null
null
null
ClCCN1CCCCC1.O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1>>O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCCN2CCCCC2)c1